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Mesoporous silica nanoparticles (MSNs) are physically and chemically stable inorganic nanomaterials that have been attracting much attention as carriers for drug delivery systems in the field of nanomedicine. In the present study, we investigated the potential of MSN vaccines that incorporate antigen peptides for use in cancer immunotherapy. In vitro experiments demonstrated that fluorescently labeled MSNs accumulated in a line of mouse dendritic cells (DC2.4 cells), where the particles localized to the cytosol. These observations could suggest that MSNs have potential for use in delivering the loaded molecules into antigen-presenting cells, thereby stimulating the host acquired immune system. In vivo experiments demonstrated prolonged survival in mice implanted with ovalbumin (OVA)-expressing lymphoma cells (E.G7-OVA cells) following subcutaneous inoculation with MSNs incorporating OVA antigen peptides. Furthermore, OVA-specific immunoglobulin G antibodies and cytotoxic T lymphocytes were detected in the serum and the spleen cells, respectively, of mice inoculated with an MSN-OVA vaccine, indicating the induction of antigen-specific responses in both the humoral and cellular immune systems. These results suggested that the MSN therapies incorporating antigen peptides may serve as novel vaccines for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management. [ABSTRACT FROM AUTHOR]

Abstract The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy. Graphical Abstract

The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is the major challenge for chemotherapy of cancer and makes the treatment benefits unsustainable. To overcome this issue, nanotechnology has been introduced and various nanocarriers have been constructed to reverse MDR in drug resistant cancer cells. Here, mesoporous silica nanoparticle (MSN-COOH) were modified with cationic anticancer peptide L-K6 (MSN@L-K6), and further loaded with doxorubicin (DOX) to construct an anticancer nano-system, MSN@L-K6@DOX. Our results showed that MSN@L-K6@DOX released DOX in pH-sensitive manner, which enable to be highly efficient in delivering drugs to tumors, counterbalancing the MDR. In addition, MSN@L-K6@DOX treatment decreased the expression level of P-glycoprotein in MCF-7/ADR cells, enhanced the intracellular accumulation of DOX, and thereafter reversed the MDR of MCF-7/ADR cells to DOX. Moreover, the MDR reversal activity of MSN@L-K6@DOX was further confirmed in xenograft mouse model, as evidenced by the decreased tumor volume and weight. These results indicate the MDR reversal activity of MSN@L-K6@DOX and may provide a novel strategy for the development of nano-based drug delivery system to overcome cancer MDR.

Mesoporous silica nanoparticles (MSNs) are highly advanced engineered particles with increased surface area and extreme adsorption capacity for various molecules. Herein, two types of MSNs were synthesized and applied as adsorbents for phosphine gas. One was without functional groups (MSN), and the other was post-modified with boric acid (MSN-BA). The structures of MSN and boric acid-modified MSN with high surface areas of about 1025 and 650 m2/g, respectively, were defined. MSN was found to have particles with sizes around 30 nm by transmission electron microscopy (TEM). In the present study, MSNs were used as an antidote to phosphorus poisoning, and zinc phosphide (phosphorus) powder was used as the toxic and lethal agent. In vivo analysis was carried out on rats to demonstrate the ability of MSNs to chemisorb phosphine gas. In the survival percentage assessment, Phos-poisoned animals were kept alive after treatment with MSNs, and the MSN-BA-treated group (dose of 5 mg/kg) was shown to have a 60 % survival rate. Blood serum analysis showed that MSNs have a high potential to alleviate organ blood damage, and serum biomarkers dropped sharply while phosphine-poisoned animals were treated with MSN-BA.

Guiqiang Qi,1 Guangyue Shi,1 Shengchao Wang,1 Haifeng Hu,2 Zhichen Zhang,1 Qiangqiang Yin,1 Zhongtao Li,1 Liguo Hao1,3 1Department of Molecular Imaging, School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang, 161006, People’s Republic of China; 2Medical Imaging Center, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161000, People’s Republic of China; 3Department of Molecular Imaging, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, 161041, People’s Republic of ChinaCorrespondence: Liguo Hao, Email haoliguo@qmu.edu.cnIntroduction: This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy.Methods: Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells.Results: Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment.Conclusion: This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.Keywords: mesoporous silica nanoparticle, drug delivery, multitherapy modality, magnetic resonance imaging, glucose oxidase

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

Coal fly ash (CFA) is an industrial byproduct produced during the production of electricity in thermal power plants from the burning of pulverized coal. It is considered hazardous due to the presence of toxic heavy metals while it is also considered valuable due to the presence of value-added minerals like silicates, alumina, and iron oxides. Silica nanoparticles' demands and application have increased drastically in the last decade due to their mesoporous nature, high surface area to volume ratio, etc. Here in the present research work, short rod-shaped, mesoporous silica nanoparticles (MSN) have been synthesized from coal fly ash by using Bacillus circulans MTCC 6811 in two steps. Firstly, CFA was kept with the bacterial culture for bioleaching for 25 days in an incubator shaker at 120 rpm. Secondly, the dissolved silica in the medium was precipitated with the 4 M sodium hydroxide to obtain a short rod-shaped MSN. The purification of the synthesized silica particle was done by treating them with 1 M HCl at 120 °C, for 90 min. The synthesized short rod-shaped MSN were characterized by UV–vis spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Particle size analyzer (PSA), Field emission scanning electron microscopy (FESEM), and transmission electron microscope. The microscopic techniques revealed the short rod-shaped mesoporous silica nanoparticles (MSN) for the final nano-silica, whose size varies from 40 to 80 nm, with an average size of 36 ± 5 nm. The XRD shows the crystalline nature of the synthesized MSN having a crystallite size of 36 nm. The FTIR showed the three characteristic bands in the range of 400–1100 cm−1, indicating the purity of the sample. The energy dispersive X-ray (EDX) showed 53.04 wt% oxygen and 43.42% Si along with 3.54% carbon in the final MSN. The particle size analyzer revealed that the average particle size is 368.7 nm in radius and the polydispersity index (PDI) is 0.667. Such a novel and economical approach could be helpful in the synthesis of silica in high yield with high purity from coal fly ash and other similar waste. [ABSTRACT FROM AUTHOR]

Nisin was loaded in mesoporous silica nanoparticles (MSN) (0, 1, 2 and 3 wt%) and incorporated into poly (lactic acid) (PLA) matrix by casting method. The mechanical property, water vapor permeability, thermal property, and antimicrobial property of PLA nanocomposite films were measured. And the internal structure of the composite film was observed through the Scanning electron microscope. Meanwhile, the kinetic of nisin releasing from food simulated solution was investigated and the migration model was established. The result showed that mesoporous silica had an effect on the mechanical and thermal property of the composite films. Both water vapor transmission rate (WVP) and oxygen permeation rate (OTR) decreased, especially for 3MSN/NI/PLA, where WVP decreased by about 9.64% and OTR decreased by 35.19%, which was beneficial to improve the preservation effect. With the addition of MSN, the amount of loaded nisin increased, and at 3MSN/NI, the nisin loading reached 88.75%, and the mesoporous silica could effectively control the release of nisin, thus prolonging the preservation effect. The release kinetic of nisin was described by Fick's law and Weibull's model. In short, the PLA nanocomposite film has the potential to be used as an antimicrobial active film by adding nisin as an antimicrobial agent. Highlights: A biodegradable antimicrobial food grade film was prepared.Nisin was added to the films as an antimicrobial agent.The ordered mesoporous structure of MSN was used as a carrier of antimicrobial agent.The film effectively inhibits E. coli and S. aureus by controlling the release of nisin.Fick's law and Weibull's model were used to describe the release kinetics of Nisin. [ABSTRACT FROM AUTHOR]

Yu Hsia,1,2 Maharajan Sivasubramanian,1 Chia-Hui Chu,1 Yao-Chen Chuang,1,3 Yiu-Kay Lai,2 Leu-Wei Lo1 1Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Zhunan, Taiwan; 2Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan; 3Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, TaiwanCorrespondence: Leu-Wei Lo, Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County 350, Zhunan, Taiwan, Tel +886-37-206-166 Ext 37115, Fax +886-37-586-440, Email lwlo@nhri.edu.tw Yiu-Kay Lai, Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, 300044, Taiwan, Tel +866-35-742-745, Email lslyk@life.nthu.edu.twBackground: Cancer multidrug resistance (MDR) is an important factor that severely affects the chemotherapeutic efficacy. Among various methods to bypass MDR, usage of cytokines, such as tumor necrosis factor alpha (TNFα) is attractive, which exerts antitumor effects of immunotherapeutic response and apoptotic/proinflammatory pathways. Nevertheless, the challenges remain how to implement targeted delivery of TNFα to reduce toxicity and manifest the involved signaling mechanism that subdues MDR.Methods: We synthesized a multifunctional nanosytem, in which TNFα covalently bound to doxorubicin (Dox)-loaded pH-responsive mesoporous silica nanoparticles (MSN) through bi-functional polyethylene glycol (TNFα-PEG-MSN-Hydrazone-Dox) as a robust design to overcome MDR.Results: The salient features of this nanoplatform are: 1) by judicious tailoring of TNFα concentration conjugated on MSN, we observed it could lead to a contrary effect of either proliferation or suppression of tumor growth; 2) the MSN-TNFα at higher concentration serves multiple functions, besides tumor targeting and inducer of apoptosis through extrinsic pathway, it inhibits the expression level of p-glycoprotein (P-gp), a cell membrane protein that functions as a drug efflux pump; 3) the enormous surface area of MSN provides for TNFα functionalization, and the nanochannels accommodate chemotherapeutics, Dox; 4) targeted intracellular release of Dox through the pH-dependent cleavage of hydrazone bonds induces apoptosis by the specific intrinsic pathway; and 5) TNFα-PEG-MSN-Hydrazone-Dox (MSN-Dox-TNFα) could infiltrate deep into the 3D spheroid tumor model through disintegration of tight junction proteins. When administered intratumorally in a Dox-resistant mouse tumor model, MSN-Dox-TNFα exhibited a synergistic therapeutic effect through the collective performances of TNFα and Dox.Conclusion: We hereby develop and demonstrate a multifunctional MSN-Dox-TNFα system with concentration-tailored TNFα that can abrogate the drug resistance mechanism, and significantly inhibit the tumor growth through both intrinsic and extrinsic apoptosis pathways, thus making it a highly potential nanomedicine translated in the treatment of MDR tumors.Graphical Abstract: Keywords: cytokine cancer therapy, tumor necrosis factor alpha, mesoporous silica nanoparticle, pH-responsive controlled release, intrinsic/extrinsic apoptosis pathways, cancer multidrug resistance

As a potential therapeutic solution for cancer, the combination of naturally occurring bioactive compounds with nanocarriers could be of great importance. In this study, a mesoporous silica nanoparticle (MSN) surface decorated with polydopamine (PDA) has been prepared using myricetin (MYR)-loaded mesoporous silica nanoparticles (MYR-MSN-PDA) as a means of drug delivery against cancer. Using dynamic light scattering (DLS), scanning electron microscopy (SEM) techniques, and Fourier-transform infrared spectroscopy (FTIR) the MYR-MSN-PDA was characterized. A cytotoxic study was then carried out by testing the MYR-MSN-PDA against normal and cancer cell lines to assess their effects on cytotoxicity. MYR-MSN-PDA were studied using flow cytometry as well as real-time quantitative PCR to determine their apoptotic properties. Furthermore, MYR-MSN-PDA was evaluated for its anti-oxidant properties as well. Compared to normal cells, MYR-MSN-PDA showed higher cytotoxicity against cancer cells, indicating that the synthesized nanoparticles do not pose any potential health risks. It is also important to note that MYR-MSN-PDA also has statistically significant level of effectiveness as an antioxidant agent in combating free radicals in both DPPH and ABTS assays (***p < 0.001). In addition, MYR-MSN-PDA at concentrations of 7, 14, and 28 µg/mL was shown to induce 6.74%, 40.1%, and 55.1% subG1 arrest in cells treated with nanoparticles, respectively, indicating that the nanoparticles can induce apoptosis. According to the results of this study, MYR-MSN-PDA synthesized in this study demonstrated potency against cancer cells in vitro, and has anti-oxidant properties which it is recommended that more research is carried out in vitro and in vivo. Overall, these results suggest that the formulation may be applicable to preclinical studies in the treatment of cancer. [ABSTRACT FROM AUTHOR]

The goal of tissue-engineered heart valves (TEHV) is to replace normal heart valves and overcome the shortcomings of heart valve replacement commonly used in clinical practice. However, calcification of TEHV is the major bottleneck to break for both clinical workers and researchers. Endothelialization of TEHV plays a crucial role in delaying valve calcification by reducing platelet adhesion and covering the calcified spots. In the present study, we loaded RunX2-siRNA and VEGF into mesoporous silica nanoparticles and investigated the properties of anti-calcification and endothelialization in vitro. Then, the mesoporous silica nanoparticle was immobilized on the decellularized porcine aortic valve (DPAV) by layer self-assembly and investigated the anti-calcification and endothelialization. Our results demonstrated that the mesoporous silica nanoparticles delivery vehicle demonstrated good biocompatibility, and a stable release of RunX2-siRNA and VEGF. The hybrid decellularized valve exhibited a low hemolysis rate and promoted endothelial cell proliferation and adhesion while silencing RunX2 gene expression in valve interstitial cells, and the hybrid decellularized valve showed good mechanical properties. Finally, the in vivo experiment showed that the mesoporous silica nanoparticles delivery vehicle could enhance the endothelialization of the hybrid valve. In summary, we constructed a delivery system based on mesoporous silica to biofunctionalized TEHV scaffold for endothelialization and anti-calcification. [ABSTRACT FROM AUTHOR]

Jianguo Sun,1,&ast; Huiling Nie,2,&ast; Panpan Pan,3,&ast; Qin Jiang,2,&ast; Chang Liu,1 Min Wang,1 Yonghui Deng,3,4 Biao Yan1 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People’s Republic of China; 2The Affiliated Eye Hospital and The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Chemistry, Fudan University, Shanghai, People’s Republic of China; 4Department of Gastroenterology and Hepatology, Zhongshan Hospital, Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghui Deng; Biao Yan, Email yhdeng@fudan.edu.cn; biao.yan@fdeent.orgBackground: Ocular vascular diseases are the major causes of visual impairment, which are characterized by retinal vascular dysfunction and robust inflammatory responses. Traditional anti-angiogenic or anti-inflammatory drugs still have limitations due to the short-acting effects. To improve the anti-angiogenic or anti-inflammatory efficiency, a dual-drug nanocomposite formulation was proposed for combined anti-angiogenic and anti-inflammatory treatment of ocular vascular diseases.Methods: : CBC-MCC@hMSN(SM) complex nanoformulation was prepared by integrating conbercept (CBC, an anti-angiogenic drug) and MCC950 (MCC, an inhibitor of inflammation) into the surface-modified hollow mesoporous silica nanoparticles (hMSN(SM)). CBC-MCC@hMSN(SM) complex nanoformulation was then characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, zeta potentials, and nitrogen adsorption-desorption measurement. CBC and MCC release profile, cytotoxicity, tissue toxicity, anti-angiogenic effects, and anti-inflammatory effects of CBC-MCC@hMSN(SM) were estimated using the in vitro and in vivo experiments.Results: CBC-MCC@hMSN(SM) complex had no obvious cytotoxicity and tissue toxicity and did not cause a detectable ocular inflammatory responses. CBC-MCC@hMSN(SM) complex was more effective than free CBC or MCC in suppressing endothelial angiogenic effects and inflammatory responses in vitro. A single intraocular injection of CBC-MCC@hMSN(SM) complex potently suppressed diabetes-induced retinal vascular dysfunction, choroidal neovascularization, and inflammatory responses for up to 6 months.Conclusion: : Combined CBC and MCC nanoformulation provides a promising strategy for sustained suppression of pathological angiogenesis and inflammatory responses to improve the treatment outcomes of ocular vascular diseases.Keywords: combined nanocomposite formulation, mesoporous silica nanoparticle, anti-angiogenesis, anti-inflammation, ocular vascular disease

Bone related infections elicit excessive inflammatory responses, progressive osteolysis, and persistent bacterial load, which impede bone regeneration. Conventional antibiotics can mitigate bacterial load; however, they fail to inhibit bone resorption and the inflammatory response. To enhance bone regeneration during bacterial infection, an optimal therapeutic strategy should not only eradicate bacteria but also inhibit inflammation and osteolysis. In this study, we fabricated a multi-biofunctional coating, designated MSNs-BMP4-EN, by covalently immobilizing mesoporous silica nanoparticles (MSNs) with human bone morphogenetic protein 4 (BMP4) and loading with enoxacin (EN) for antibacterial effect with inhibiting inflammation and osteolysis. Antimicrobial assessments revealed that MSNs-BMP4-EN markedly obstructed bacterial adhesion and colonization. Subsequent in vitro assessments demonstrated that it facilitated osteogenic differentiation of bone mesenchymal stem cell and impeded early osteoclastogenesis. Moreover, MSNs-BMP4-EN effectively restrained the secretion of pro-inflammatory mediators, thereby counteracting the infection-induced inflammatory milieu and promoting bone regeneration. Collectively, these findings indicate that MSNs-BMP4-EN exhibits excellent antibacterial, anti-inflammatory, and bone resorption inhibitory attributes during initial stages of bone-related infection, thereby further improving bone regeneration. As a result, this bioactive nanocomposite has excellent prospects for treating bone infections.

[Display omitted] In recent years, injectable stimuli-sensitive hydrogels are employed as suitable drug delivery carriers for the release of various anti-cancer drugs. However, large pore size of the microporous hydrogel trigger release of small molecular anticancer drug that limits hydrogel application in cancer therapy. Therefore, introducing reinforcing fillers such as mesoporous silica nanoparticles (MSNs) can not only load different type of anticancer drugs but also prevent the premature release of drugs due to the strengthening of the networks. Furthermore, high specific surface area, suitable size, large pore volume, and stable physicochemical properties of MSNs can improve the therapeutic efficacy. In this study, to sustain the release of hydrophobic anticancer drug, camptothecin (CPT) was loaded into MSNs, and then imbibed into the physiological stimuli-sensitive poly(ethylene glycol)-poly(β-aminoester urethane) (PAEU) hydrogels. MSN-imbibed PAEU hydrogels exhibited prolonged release of CPT than MSNs and PAEU hydrogel alone. Furthermore, MSN-imbibed PAEU copolymers form stable viscoelastic gel depot into the subcutaneous layers of Sprague-Dawley rats and found to be safe and not induced toxicity to healthy organs, implying biodegradability and safety of the hydrogels. Interestingly, CPT-loaded hydrogels shown dose-dependent toxicity to A549 and B16F10 cells. These results demonstrated that MSN-imbibed PAEU hydrogel with biocompatible, biodegradable, and in situ gel forming property could be a useful drug delivery depot for sustained release of anticancer drugs. [ABSTRACT FROM AUTHOR]

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and −35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release. [ABSTRACT FROM AUTHOR]

The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN-SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation-enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin-4, indicates the opening of tight junction. Moreover, MSN-SH(E)-associated reprogramming of M2 macrophages to M1-like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)-loaded nanovector (MMC@MSN-SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN-y, TGF-/1, and TNF-a. These observations substantiated the significance of MMC@MSN-SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non-muscle invasive bladder cancer (NMIBC) dueto its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure. [ABSTRACT FROM AUTHOR]

Liver cancer, especially hepatocellular carcinoma, is an important cause of cancer-related death, and its incidence is increasing worldwide. Nano drug delivery systems have shown great promise in the treatment of cancers. In order to improve their therapeutic efficacy, it is very important to realize the high accumulation and effective release of drugs at the tumor site. In this manuscript, using doxorubicin (DOX) as a model drug, CD13-targeted mesoporous silica nanoparticles coated with NGR-peptide-modified pegylated carboxymethyl chitosan were constructed (DOX/MSN-CPN). DOX/MSN-CPN comprises a spherical shape with an obvious capping structure and a particle size of 125.01 ± 1.52 nm. With a decrease in pH, DOX/MSN-CPN showed responsive desorption from DOX/MSN-CPN and pH-responsive release of DOX was observed. Meanwhile, DOX/MSN-CPN could be efficiently absorbed through NGR-mediated internalization in vitro and could efficiently deliver DOX to tumor tissues with long accumulation times in vivo, suggesting good active targeting properties. Moreover, significant tumor inhibition has been observed in antitumor studies in vivo. This study provides a strategy of utilizing DOX/MSN-CPN as a nano-platform for drug delivery, which has superb therapeutic efficacy and safety for the treatment of hepatocellular carcinoma both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Abstract The characteristics of global prevalence and high recurrence of bladder cancer has led numerous efforts to develop new treatments. The spontaneous voiding and degradation of the chemodrug hamper the efficacy and effectiveness of intravesical chemotherapy following tumor resection. Herein, the externally thiolated hollow mesoporous silica nanoparticles (MSN‐SH(E)) is fabricated to serve as a platform for improved bladder intravesical therapy. Enhanced mucoadhesive effect of the thiolated nanovector is confirmed with porcine bladder. The permeation‐enhancing effect is also verified, and a fragmented distribution pattern of a tight junction protein, claudin‐4, indicates the opening of tight junction. Moreover, MSN‐SH(E)‐associated reprogramming of M2 macrophages to M1‐like phenotype is observed in vitro. The antitumor activity of the mitomycin C (MMC)‐loaded nanovector (MMC@MSN‐SH(E)) is more effective than that of MMC alone in both in vitro and in vivo. In addition, IHC staining is used to analyze IFN‐γ, TGF‐β1, and TNF‐α. These observations substantiated the significance of MMC@MSN‐SH(E) in promoting anticancer activity, holding the great potential for being used in intravesical therapy for non‐muscle invasive bladder cancer (NMIBC) due to its mucoadhesivity, enhanced permeation, immunomodulation, and prolonged and very efficient drug exposure.

Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (>64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Background: Sonodynamic therapy (SDT) may be a new hopeful non-invasive method for cancer treatment, which incorporates a combination of low-intensity ultrasound and a sonosensitive chemical. The goal of this study was to evaluate the effect of dual-frequency sonication (1 and 3 MHz) and injected Hematoporphyrin encapsulated in mesoporous silica nanoparticles (HP-MSNs) as a sensitizer in the treatment of mice grafted with breast adenocarcinoma.Methods: In this research, one hundred and thirty-two female mice with grafted breast adenocarcinoma were separated into 22 groups including control, sham, 4 groups of sonication 1 or 3 MHz (1 and 2 W/cm2), and 16 groups of SDT with Hematoporphyrin (HP) and HP-MSNs (2.5 and 5 mg/kg). The tumor growth factors and tumor grading were used to assess the treatment management.Results: The results indicate that dual-frequency sonication has a delayed effect on tumor growth. The required time of T5 to the initial volume in all groups of SDT with HP (5 mg/kg) was greater than that in the control group (P

Peiqi Zhao,1,&ast; Yuanlin Xu,2,&ast; Wei Ji,3 Lanfang Li,1 Lihua Qiu,1 Shiyong Zhou,1 Zhengzi Qian,1 Huilai Zhang1 1Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China; 2Department of Lymphatic Comprehensive Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Public Laboratory, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peiqi Zhao; Huilai ZhangDepartment of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of ChinaTel +86-22-23340123Email peiqizhao@126.com; zhanghltch@163.comPurpose: Cancer vaccines are a promising therapeutic approach in cancer immunotherapy and can inhibit tumor growth and prevent tumor recurrence and metastasis by activating a sustained antitumor immunoprotective effect. However, the therapeutic effect of cancer vaccines is severely weakened by the low immunogenicity of cancer antigens and the immunosuppressive microenvironment in tumor tissues.Methods: Here, we report a novel hybrid membrane nanovaccine, composed of mesoporous silica nanoparticle as a delivery carrier, hybrid cell membranes obtained from dendritic cells and cancer cells, and R837 as an immune adjuvant (R837@HM-NPs). We investigated the anti-tumor, tumor recurrence and metastasis prevention abilities of R837@HM-NPs and their mechanisms of action through a series of in vivo and ex vivo experiments.Results: R837@HM-NPs not only provide effective antigenic stimulation but are also a durable supply of the immune adjuvant R837. In addition, R837@HM-NPs promote antigen endocytosis into dendritic cells via various receptor-mediated pathways. Compared with HM-NPs or R837@HM-NPs, R837@HM-NPs in combination with an immune checkpoint blockade showed stronger antitumor immune responses in inhibiting tumor growth, thus eliminating established tumors, and rejecting re-challenged tumors by regulating the immunosuppressive microenvironment and immunological memory effect.Conclusion: These findings suggest that the hybrid membrane nanovaccine in combination with immune checkpoint blockade is a powerful strategy to enhance antitumor immunotherapy without concerns of systemic toxicity.Keywords: hybrid membrane, immune checkpoint blockade, immunotherapy, mesoporous silica nanoparticle, nanovaccine

The goal of tissue-engineered heart valves (TEHV) is to replace normal heart valves and overcome the shortcomings of heart valve replacement commonly used in clinical practice. However, calcification of TEHV is the major bottleneck to break for both clinical workers and researchers. Endothelialization of TEHV plays a crucial role in delaying valve calcification by reducing platelet adhesion and covering the calcified spots. In the present study, we loaded RunX2-siRNA and VEGF into mesoporous silica nanoparticles and investigated the properties of anti-calcification and endothelialization in vitro. Then, the mesoporous silica nanoparticle was immobilized on the decellularized porcine aortic valve (DPAV) by layer self-assembly and investigated the anti-calcification and endothelialization. Our results demonstrated that the mesoporous silica nanoparticles delivery vehicle demonstrated good biocompatibility, and a stable release of RunX2-siRNA and VEGF. The hybrid decellularized valve exhibited a low hemolysis rate and promoted endothelial cell proliferation and adhesion while silencing RunX2 gene expression in valve interstitial cells, and the hybrid decellularized valve showed good mechanical properties. Finally, the in vivo experiment showed that the mesoporous silica nanoparticles delivery vehicle could enhance the endothelialization of the hybrid valve. In summary, we constructed a delivery system based on mesoporous silica to biofunctionalized TEHV scaffold for endothelialization and anti-calcification.

As injected drugs finally diffuse to the target cells, a quantitative understanding of the diffusion behavior of drug molecules or drug carriers is essential for the determination of their efficacy or optimal doses. Here, we propose a method for determining the diffusivity (D, diffusion coefficient) of drug carriers in tissue-mimicking collagen in the lab-on-a-chip (LOC) platform and predict their spatiotemporal distribution using the calculated D. By controlling the concentrations of fluorescent mesoporous silica nanoparticles (MSNs) in each channel, the diffusion of fluorescent MSNs was induced and fluorescence gradients in collagen were produced and captured as images. The D of the MSNs by size was obtained by fitting the fluorescence profiles to the solution of Fick's second law. The D of MSNs varied by size from 2.98 × 10–10 m2/s (MSNs of 10 nm) to 1.14 × 10–11 m2/s (MSNs of 1 μm). The spatiotemporal profiles of MSNs were calculated using the obtained D, and it was demonstrated that the concentration of MSNs with a size >200 nm at 100 μm from the gel–liquid interface will remain <50% of that in the vessel-mimicking channel even after 3 h. As the analysis and prediction procedures based on fluorescence profile image processing and a least-squares fit to the solution are relatively simple, our results can be extended to various studies to narrow the gap between in vitro tests and animal experiments in drug or particle transport research through the calculation of the diffusion coefficient of drug candidates before animal experiments and might replace some parts of animal experiments of drug delivery studies. [ABSTRACT FROM AUTHOR]

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose. [ABSTRACT FROM AUTHOR]

New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug. [ABSTRACT FROM AUTHOR]

Systemic infections caused by life-threatening pathogens represent one of the main factors leading to clinical death. In this study, we developed a pathogen infection-responsive and macrophage endoplasmic reticulum-targeting nanoplatform to alleviate systemic infections. The nanoplatform is composed of large-pore mesoporous silica nanoparticles (MSNs) grafted by an endoplasmic reticulum-targeting peptide, and a pathogen infection-responsive cap containing the reactive oxygen species-cleavable boronobenzyl acid linker and bovine serum albumin. The capped MSNs exhibited the capacity to high-efficiently load the antimicrobial peptide melittin, and to rapidly release the cargo triggered by H2O2 or the pathogen-macrophage interaction system, but had no obvious toxicity to macrophages. During the interaction with pathogenic Candida albicans cells and macrophages, the melittin-loading nanoplatform MSNE+MEL+TPB strongly inhibited pathogen growth, survived macrophages, and suppressed endoplasmic reticulum stress together with pro-inflammatory cytokine secretion. In a systemic infection model, the nanoplatform efficiently prevented kidney dysfunction, alleviated inflammatory symptoms, and protected the mice from death. This study developed a macrophage organelle-targeting nanoplatform for treatment of life-threatening systemic infections. [ABSTRACT FROM AUTHOR]

Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/β-catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over-activated Wnt pathway, while Wnt16-deficient mice has a more severe Knee OA. However, the efficacy of direct intra-TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small-molecule drugs such as Wnt16 usually exhibit short-lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double-layer slow-release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro-cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over-activation of the Wnt/β-catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Conditions affecting the brain are the second leading cause of death globally. One of the main challenges for drugs targeting brain diseases is passing the blood-brain barrier (BBB). Here, the effectiveness of mesoporous silica nanostars (MSiNSs) with two different spike lengths to cross an in vitro BBB multicellular model was evaluated and compared to spherical nanoparticles (MSiNP). A modified sol-gel single-micelle epitaxial growth was used to produce MSiNS, which showed no cytotoxicity or immunogenicity at concentrations of up to 1 μg mL -1 in peripheral blood mononuclear and neuronal cells. The nanostar MSiNS effectively penetrated the BBB model after 24 h, and MSiNS-1 with a shorter spike length (9 ± 2 nm) crossed the in vitro BBB model more rapidly than the MSiNS-2 with longer spikes (18 ± 4 nm) or spherical MSiNP at 96 h, which accumulated in the apical and basolateral sides, respectively. Molecular dynamic simulations illustrated an increase in configurational flexibility of the lipid bilayer during contact with the MSiNS, resulting in wrapping, whereas the MSiNP suppressed membrane fluctuations. This work advances an effective brain drug delivery system based on virus-like shaped MSiNS for the treatment of different brain diseases and a mechanism for their interaction with lipid bilayers.

Abstract New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and −35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release.

Mesoporous silica nanoparticles (MSNs) are widely used in many biomedical applications and clinical fields. However, the applications of MSNs are limited by their severe toxicity. Apigenin (AG) has demonstrated pharmacological effects with low toxicity. The aim of this study was to clarify the role of AG in the progression of MSNs-induced renal injury. BALB/c mice and NRK-52E cells were exposed to MSNs with or without AG. AG protected mice and NRK-52E cells from the MSNs-induced pathological variations in renal tissues and decreased cell viability. AG significantly reduced the levels of serum blood urea nitrogen (BUN) and serum creatinine (Scr), upregulated the levels of superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), and improved the pathological changes of the kidney in MSNs-treated mice. The protective effects of AG were associated with its ability to increase the levels of antioxidants, reduce the accumulation of ROS, and inhibit the expression of the inflammatory mediators (TNF-α, IL-6). In addition, AG treatment upregulated the activity of FOXO3a, increased the level of IkBα, and reduced the nuclear translocation of NF-κB, which ultimately alleviated MSNs-induced inflammation. Nuclear FOXO3a translocation also triggered antioxidant gene transcription and protected nephrocyte from oxidative damage. However, knockdown of FOXO3a significantly blocked the protective effects of AG. These findings suggested that AG could be a promising therapeutic strategy for MSNs-induced nephrotoxicity, and this protective effect might be related to the suppression of oxidative stress and inflammation via the FOXO3a/NF-κB pathway. [ABSTRACT FROM AUTHOR]

This work was developed to the effects of biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) on lymph node metastasis from oral squamous cell carcinoma. Mesoporous silica nanoparticles loaded with 5-FU (MSN-5-FU) were prepared first. Subsequently, the outer membrane vesicles (OMV) of Escherichia coli were collected to wrap MSN-5-FU, and then OMVs-MSN-5-FU was prepared. It was then immersed in artificial gastric juice and artificial intestinal juice to explore the drug release rate. Next, the effects of different concentrations of the nano-drug delivery systems on the proliferation activity of oral squamous carcinoma cell line KOSC-2 cl3-43 were analyzed. Tumor-bearing nude mice models were prepared by injecting human tongue squamous cell carcinoma cells Tca8113 into BALB/c-nu nude mice. They were injected with the OMVs-MSN-5-FU nano drug carrier system, and peri-carcinoma tissue and cervical lymph node tissue were harvested to observe morphological changes by Hematoxylin – eosin (HE) staining. The scanning electron microscope (SEM) results showed that all MSN, MSN-5-FU, OMV, and OMV-MSN-5-FU were spherical and uniformly distributed, with particle sizes of about 60nm, 80nm, 90nm, and 140nm, respectively. Among them, OMV had a directional core-shell structure. The cumulative drug release rates of artificial gastric juice in 48 hours were 61.2 ± 2.3% and 26.5 ± 3.1%, respectively. The 48 hours cumulative drug release rates of artificial intestinal juice were 70.5 ± 6.3% and 32.1 ± 3.8%, respectively. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. After injection of OMVS-MSN-5-FU, the number of cancer cells was significantly reduced and cervical lymph node metastasis was significantly controlled. HE staining results showed that OMVS-MSN-5-FU injection reduced the number of stained cells. Dense lymphocytes were clearly observed in the cortex of neck lymphocytes. The OMVs-MSN-5-FU drug delivery system can slow down the drug release rate, significantly inhibit the proliferation activity of oral squamous cancer cells, and control the metastasis of cancer cells to cervical lymph nodes. [ABSTRACT FROM AUTHOR]

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study. [ABSTRACT FROM AUTHOR]

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, as an important part in innate immunity, has recently emerged as a promising target for improving tumor therapy. Manganese ions (Mn2+) are an emerging agonist in the cGAS-STING pathway with multifaceted advantages, however manganese-based nanoparticles alone as the Mn2+ source have shown limited activity in eliciting anti-tumor immune responses compared to conventional organic STING agonists, and the underlying mechanism of the suboptimal efficiency remains unclear. Here, we demonstrate that intratumoral iron ions attenuate manganese-induced anti-tumor STING activation, and that the utilization of deferoxamine (DFO), an iron chelator that depletes intratumoral iron ions, effectively increases the intracellular accumulation of Mn2+ and thus promoted the STING activation efficiency of a hyaluronic acid modified manganese carbonate-silica hybrid nanoparticle (DS@Mn-H) in macrophages. The mechanism study suggests that the addition of DFO inhibited the expression of ferroportin (FPN), which serves as a Mn2+ exporter to reduce intracellular Mn2+ level. The synergistic effect of DS@Mn-H and DFO achieved excellent anti-tumor activities in a mouse colon carcinoma model. This work provides new insights on improving the Mn-based metallo-immunotherapy of cancer. [Display omitted] • Tumor tissues have higher iron content than adjacent normal tissues. • High iron level reduces Mn2+ accumulation and associated STING activation in macrophages. • MnCO 3 modified dendritic mesoporous silica nanoparticles (DS@Mn) improve intracellular Mn2+ delivery efficiency. • DFO, an iron chelator, further enhances Mn2+ accumulation and STING activation of DS@Mn. • The synergistic effect of DS@Mn and DFO achieves excellent anti-tumor immune response in a mouse colon carcinoma model. [ABSTRACT FROM AUTHOR]

Despite its prominent therapeutic efficacy, chemotherapy has raised serious concerns due to the severe adverse effects and multidrug resistance evoked, which propels the search for safe and green therapeutic agents. BAMLET (bovine α-lactalbumin made lethal against tumor cell) is a well-known protein-based anticancer agent of selective tumoricidal activity. Here, we prepared oleic acid-modified mesoporous silica nanoparticles (OA-MSNs) conjugated with bovine α-lactalbumin, a lipoprotein complex resembling BAMLET formed on the surface of MSNs (MSN-BAMLET) to load the anticancer drug of docetaxel (DTX). Compared to that of OA-MSNs/DTX, the obtained MSN-BAMLET/DTX with a sustained and pH-responsive drug release behaviors exhibited good biocompatibility and enhanced cytotoxic effect against cancer cells. Moreover, the presence of lipoprotein complex in MSN-BAMLET contributed to the improved dispersion of the composite in solution and the inhibitory effect on the migration of cancer cells. Furthermore, the adsorption profiles of protein corona on the obtained nanoparticles were analyzed. It was found that the marked low amount and abundance of plasma proteins were adsorbed on the α-lactalbumin coated siliceous composite demonstrated its long circulation property. Finally, in vivo study showed that MSN-BAMLET/DTX contributed to the effective cancer ablation and the prolonged survival. Therefore, the constructed MSN-BAMLET of the mesoregular structure and peculiar tumoricidal effect provides a manipulable nanoplatform as drug nanocarrier for therapeutic applications.

This work was developed to the effects of biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) on lymph node metastasis from oral squamous cell carcinoma. Mesoporous silica nanoparticles loaded with 5-FU (MSN-5-FU) were prepared first. Subsequently, the outer membrane vesicles (OMV) of Escherichia coli were collected to wrap MSN-5-FU, and then OMVs-MSN-5-FU was prepared. It was then immersed in artificial gastric juice and artificial intestinal juice to explore the drug release rate. Next, the effects of different concentrations of the nano-drug delivery systems on the proliferation activity of oral squamous carcinoma cell line KOSC-2 cl3-43 were analyzed. Tumor-bearing nude mice models were prepared by injecting human tongue squamous cell carcinoma cells Tca8113 into BALB/c-nu nude mice. They were injected with the OMVs-MSN-5-FU nano drug carrier system, and peri-carcinoma tissue and cervical lymph node tissue were harvested to observe morphological changes by Hematoxylin – eosin (HE) staining. The scanning electron microscope (SEM) results showed that all MSN, MSN-5-FU, OMV, and OMV-MSN-5-FU were spherical and uniformly distributed, with particle sizes of about 60nm, 80nm, 90nm, and 140nm, respectively. Among them, OMV had a directional core-shell structure. The cumulative drug release rates of artificial gastric juice in 48 hours were 61.2 ± 2.3% and 26.5 ± 3.1%, respectively. The 48 hours cumulative drug release rates of artificial intestinal juice were 70.5 ± 6.3% and 32.1 ± 3.8%, respectively. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. After injection of OMVS-MSN-5-FU, the number of cancer cells was significantly reduced and cervical lymph node metastasis was significantly controlled. HE staining results showed that OMVS-MSN-5-FU injection reduced the number of stained cells. Dense lymphocytes were clearly observed in the cortex of neck lymphocytes. The OMVs-MSN-5-FU drug delivery system can slow down the drug release rate, significantly inhibit the proliferation activity of oral squamous cancer cells, and control the metastasis of cancer cells to cervical lymph nodes.

Peiqi Zhao, Lihua Qiu, Shiyong Zhou, Lanfang Li, Zhengzi Qian, Huilai Zhang Department of Lymphoma, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Huilai ZhangDepartment of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, 24 Huanhu West Road, Hexi District, Tianjin, 300060, People’s Republic of ChinaTel +86-22-23340123Email zhlwgq@126.comPurpose: Although anti-programmed cell death protein 1 antibody (aPD1) immunotherapy and chemotherapy has made much progress in the treatment of melanoma, the efficacy still needs to be further improved.Methods: Cancer treatment has been greatly enhanced by the use of nanotechnology. Cancer cell membrane (CCM)-camouflaged nanoparticles have shown promising potential in tumor therapy due to their excellent homologous-targeting ability, long blood circulation and immune escape. This work presents a biocompatible and tumor acidic environmental responsive CCM-camouflaged mesoporous silica nanoparticle (CMSN) that is loaded with dacarbazine (DTIC) and combined with aPD1 to achieve better antitumor efficacy.Results: In vitro cell experiments demonstrated that DTIC@CMSN exhibits a better anti-tumor killing efficiency and a stronger ability to promote the apoptosis of tumor cells than free DTIC. In vivo antitumor results demonstrated that combination therapy of DTIC@CMSN chemotherapy and aPD1 immunotherapy remarkably suppress the melanoma growth and prolong survival time due to highly selective tumor killing, activation of tumor-specific T cells, and regulation of the immunosuppressive tumor microenvironment. In addition, safety evaluation studies of DTIC@CMSN also demonstrate their increased tumor accumulation and decreased systemic toxicity.Conclusion: This study provides a promising nano-platform for the combination of chemotherapy with immunotherapy, which is potentially useful for the treatment of melanoma.Keywords: anti-PD-1, cancer cell membrane, cancer immunotherapy, melanoma, mesoporous silica nanoparticle

Abstract Background A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSN) grafted with poly-L-glycolic acid (PGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, this study aimed to investigate the delivery of CHX-loaded/MSN-PGA nanoparticles through demineralized dentin tubules and how these nanoparticles interact with tooth dentin after mixing with commercial dentin adhesive for potential clinical application. Results Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PGA. An increase in the percentage of drug encapsulation efficiency from 81 to 85% in CHX loaded/MSN and 92–95% in CHX loaded/MSN-PGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 days), the relative microbial viability significantly decreased by increasing the CHX content (P 80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), the significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive. Conclusions A pH-sensitive CHX release response was noted when loaded in MSN grafted PGA nanoparticles. The formulated drug-loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.

[Display omitted] • A novel lymph node (LN)-targeted delivery system of FK506 based on mesoporous silicon nanoparticles (MSNs) was prepared. • MSNs provide sufficient storage space for FK506 with hydrophobicity and improve the drug loading efficiency. • MECA79 antibody-modified MSNs have the ability to target LNs and increase the FK506 level in LNs. • The LN-targeted delivery system of FK506 is associated with better therapeutic outcomes on a skin transplantation model. Tacrolimus (FK506) is an effective therapeutic for transplant rejection in clinical practice, primarily inhibiting rejection by suppressing the activation and proliferation of allogeneic T cells in the lymph nodes (LNs). However, conventional administration methods face challenges in directly delivering free FK506 to the LNs. In this study, we introduce a novel LN-targeted delivery system based on mesoporous silica nanoparticles (MSNs-FK506-MECA79). These particles were designed to selectively target high endothelial venules in LNs; this was achieved through surface modification with MECA79 antibodies. Their mean size and zeta potential were 201.18 ± 5.98 nm and − 16.12 ± 0.36 mV, respectively. Our findings showed that MSNs-FK506-MECA79 could accumulate in LNs and increase the local concentration of FK506 from 28.02 ± 7.71 ng/g to 123.81 ± 76.76 ng/g compared with the free FK506 treatment group. Subsequently, the therapeutic efficacy of MSNs-FK506-MECA79 was evaluated in a skin transplantation model. The treatment with MSNs-FK506-MECA79 could lead to a decrease in the infiltration of T cells in the grafts, a reduction in the grade of rejection, and a significant prolongation of survival. Consequently, this study presents a promising strategy for the active LN-targeted delivery of FK506 and improving the immunotherapeutic effects on transplant rejection. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is the major challenge for chemotherapy of cancer and makes the treatment benefits unsustainable. To overcome this issue, nanotechnology has been introduced and various nanocarriers have been constructed to reverse MDR in drug resistant cancer cells. Here, mesoporous silica nanoparticle (MSN-COOH) were modified with cationic anticancer peptide L-K6 (MSN@L-K6), and further loaded with doxorubicin (DOX) to construct an anticancer nano-system, MSN@L-K6@DOX. Our results showed that MSN@L-K6@DOX released DOX in pH-sensitive manner, which enable to be highly efficient in delivering drugs to tumors, counterbalancing the MDR. In addition, MSN@L-K6@DOX treatment decreased the expression level of P-glycoprotein in MCF-7/ADR cells, enhanced the intracellular accumulation of DOX, and thereafter reversed the MDR of MCF-7/ADR cells to DOX. Moreover, the MDR reversal activity of MSN@L-K6@DOX was further confirmed in xenograft mouse model, as evidenced by the decreased tumor volume and weight. These results indicate the MDR reversal activity of MSN@L-K6@DOX and may provide a novel strategy for the development of nano-based drug delivery system to overcome cancer MDR. [ABSTRACT FROM AUTHOR]

[Display omitted] Controlling the drug release and restricting its presence in healthy organs is extremely valuable. In this study, mesoporous silica nanoparticles (MSN) as the core, loaded with paclitaxel (PTX), were coated with a non-porous silica shell functionalized with disulfide bonds. The nanoparticles were further coated with polyethylene glycol (PEG) via disulfide linkages. We analyzed the physicochemical properties of nanoparticles, including hydrodynamic size via Dynamic Light Scattering (DLS), zeta potential, X-ray Diffraction (XRD) patterns, Fourier-Transform Infrared (FTIR) spectra, and imaging through Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). The drug release profile in two distinct glutathione (GSH) concentrations of 2 µM and 10 µM was measured. The cellular uptake of nanoparticles by MCF-7 cell line was determined using Confocal Laser Scanning Microscopy (CLSM) images and flow cytometry. Furthermore, the cell viability and the capability of nanoparticles to induce apoptosis in MCF-7 cell line were studied using the MTT assay and flow cytometry, respectively. Our investigations revealed that the release of PTX from the drug delivery system was redox-responsive. Also, results indicated an elevated level of cellular uptake and efficient induction of apoptosis, underscoring the promising potential of this redox-responsive drug delivery system for breast cancer therapy. [ABSTRACT FROM AUTHOR]

To improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS). ELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo. The targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug. Collectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer. [Display omitted] • Elesclomol is an effective mitochondrion-targeting agent for treatment of wide variety of cancers. • Elesclomol can produce high levels of ROS within the organelle leading to cancer cell death. • Combination of Elesclomol with several therapeutic agents is also an alternative way to augment its anticancer potency. [ABSTRACT FROM AUTHOR]

Liver cancer, especially hepatocellular carcinoma, is an important cause of cancer-related death, and its incidence is increasing worldwide. Nano drug delivery systems have shown great promise in the treatment of cancers. In order to improve their therapeutic efficacy, it is very important to realize the high accumulation and effective release of drugs at the tumor site. In this manuscript, using doxorubicin (DOX) as a model drug, CD13-targeted mesoporous silica nanoparticles coated with NGR-peptide-modified pegylated carboxymethyl chitosan were constructed (DOX/MSN-CPN). DOX/MSN-CPN comprises a spherical shape with an obvious capping structure and a particle size of 125.01 ± 1.52 nm. With a decrease in pH, DOX/MSN-CPN showed responsive desorption from DOX/MSN-CPN and pH-responsive release of DOX was observed. Meanwhile, DOX/MSN-CPN could be efficiently absorbed through NGR-mediated internalization in vitro and could efficiently deliver DOX to tumor tissues with long accumulation times in vivo, suggesting good active targeting properties. Moreover, significant tumor inhibition has been observed in antitumor studies in vivo. This study provides a strategy of utilizing DOX/MSN-CPN as a nano-platform for drug delivery, which has superb therapeutic efficacy and safety for the treatment of hepatocellular carcinoma both in vivo and in vitro.

Stem cell (SC)-based therapies hold the potential to revolutionize therapeutics by enhancing the body's natural repair processes. Currently, there are only three SC therapies with marketing authorization within the European Union. To optimize outcomes, it is important to understand the biodistribution and behavior of transplanted SCs in vivo. A variety of imaging agents have been developed to trace SCs; however, they mostly lack the ability to simultaneously monitor the SC function and biodistribution at high resolutions. Here, we report the synthesis and application of a nanoparticle (NP) construct consisting of a gold NP core coated with rhodamine B isothiocyanate (RITC)-doped mesoporous silica (AuMS). The MS layer further contained a thiol-modified internal surface and an amine-modified external surface for dye conjugation. Highly fluorescent AuMS of three different sizes were successfully synthesized. The NPs were non-toxic and efficiently taken up by limbal epithelial SCs (LESCs). We further showed that we can functionalize AuMS with a reactive oxygen species (ROS)-sensitive fluorescent dye using two methods, loading the probe into the mesopores, with or without additional capping by a lipid bilayer, and by covalent attachment to surface and/or mesoporous-functionalized thiol groups. All four formulations displayed a ROS concentration-dependent increase in fluorescence. Further, in an ex vivo SC transplantation model, a combination of optical coherence tomography and fluorescence microscopy was used to synergistically identify AuMS-labeled LESC distribution at micrometer resolution. Our AuMS constructs allow for multimodal imaging and simultaneous ROS sensing of SCs and represent a promising tool for in vivo SC tracing. [ABSTRACT FROM AUTHOR]

Premature leakage of drugs into the bloodstream remains a problem in the process of drug delivery, resulting in higher toxic and side effects on normal tissue cells. Novel drug carriers enabling effective drug accumulation in the tumor site have got much attention of researchers. Poly (methyl acrylic acid diisopropyl amino ethyl ester) (PDPA) is a polymer with pH-sensitive response, the diisopropylamine in the side chains are protonated in an acidic environment, resulting in its changing from hydrophobic to hydrophilic. PDPA was grafted onto the surface of mesoporous silica nanoparticles (MSNs) by atom transfer radical polymerization (ATRP) reaction. Then folic acid (FA) was introduced onto PDPA as a targeting ligand for enabling the drug carrier to enter tumor cells effectively. Simultaneously poly [di (ethylene glycol) methyl ether methacrylate-co-oligo (ethylene glycol) methacrylate]-b-poly[methyl acrylic acid diisopropyl amino ethyl ester] (P(MEO2MA90-co-OEGMA10)-b-PDPA10) with dual sensitivity of temperature and pH was synthesized and the lower critical solution temperatures (LCST) of the polymer was adjusted to 44 ℃ by adjusting the proportion of three monomers. A drug carrier with a core-shell structure was self-assembled through hydrophobic force by covering the later polymer on the surface of MSNs-PDPA-FA. Finally, the drug release kinetics of the carrier was studied by using doxorubicin(DOX) as a model drug, and the result showed that the total leakage of the model drug DOX was less than 10% after 48 h in normal physiological environment (pH=7.4, 37 ℃). However, when the pH value was changed to 5.0 at 44 ℃, the shell was dissociated from the core and the drug was released. Then, the drug was released rapidly within 5 h and the cumulative drug release could reach to 65% in 48 h. Therefore, this research was expected to construct a shielding system based on the pH/temperature dualresponsive polymer, which could be used to avoid premature exposure of certain functional groups or molecules to the normal physiological environment, and it could also prevent the premature release of drugs in the normal tissues. [ABSTRACT FROM AUTHOR]

Background: Sonodynamic therapy (SDT) may be a new hopeful non-invasive method for cancer treatment, which incorporates a combination of low-intensity ultrasound and a sonosensitive chemical. The goal of this study was to evaluate the effect of dual-frequency sonication (1 and 3 MHz) and injected Hematoporphyrin encapsulated in mesoporous silica nanoparticles (HPMSNs) as a sensitizer in the treatment of mice grafted with breast adenocarcinoma. Methods: In this research, one hundred and thirty-two female mice with grafted breast adenocarcinoma were separated into 22 groups including control, sham, 4 groups of sonication 1 or 3 MHz (1 and 2 W/cm² ), and 16 groups of SDT with Hematoporphyrin (HP) and HP-MSNs (2.5 and 5 mg/kg). The tumor growth factors and tumor grading were used to assess the treatment management. Results: The results indicate that dual-frequency sonication has a delayed effect on tumor growth. The required time of T5 to the initial volume in all groups of SDT with HP (5 mg/kg) was greater than that in the control group (P<0.05). It was observed that SDT with an injection of HPMSNs was effective in delaying tumor growth and the time of T2 and T5 was higher than that of other groups (P<0.05). This group had Grade II (intermediate), while others had Grade III (high) malignancy in the histological study of mice breast adenocarcinoma. Conclusion: Our results reveal that dual-frequency SDT therapy with HP-MSN has a delaying tumor growth effect on mice breast adenocarcinoma. Hence, the expansion of minimally invasive methods such as SDT is necessary. [ABSTRACT FROM AUTHOR]