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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.

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.

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.

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.

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.

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.

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.

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Background: Liver fibrosis, as a common and refractory disease, is challenging to treat due to the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4), which is expected to have good potential effects against liver fibrosis. However, IMB16-4 is water-insoluble and has very low bioavailability. Methods: Mesoporous silica nanoparticles (MSNs) were selected as drug carriers for the purpose of increasing the dissolution of IMB16-4, as well as improving its oral bioavailability and inhibiting liver fibrosis. The physical states of IMB16-4 and IMB16-4-MSNs were investigated using nitrogen adsorption, thermogravimetric analysis (TGA), HPLC, UV-Vis, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). Results: The results show that MSNs enhanced the dissolution rate of IMB16-4 significantly. IMB16-4-MSNs reduced cytotoxicity at high concentrations of IMB16-4 on human hepatic stellate cells LX-2 cells and improved oral bioavailability up to 530% compared with raw IMB16-4 on Sprague–Dawley (SD) rats. In addition, IMB16-4-MSNs repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers, including α-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β1) and matrix metalloproteinase-2 (MMP2) in LX-2 cells. Conclusions: These results provided powerful information on the use of IMB16-4-MSNs for the treatment of liver fibrosis in the future.

Macrophages line the walls of microvasculature, extending processes into the blood flow to capture foreign invaders, including nano-scale materials. Using mesoporous silica nanoparticles (MSNs) as a model nano-scale system, we show the interplay between macrophages and MSNs from initial uptake to intercellular trafficking to neighboring cells along microtubules. The nature of cytoplasmic bridges between cells and their role in the cell-to-cell transfer of nano-scale materials is examined, as is the ability of macrophages to function as carriers of nanomaterials to cancer cells. Both direct administration of nanoparticles and adoptive transfer of nanoparticle-loaded splenocytes in mice resulted in abundant localization of nanomaterials within macrophages 24 h post-injection, predominately in the liver. While heterotypic, trans-species nanomaterial transfer from murine macrophages to human HeLa cervical cancer cells or A549 lung cancer cells was robust, transfer to syngeneic 4T1 breast cancer cells was not detected in vitro or in vivo. Cellular connections and nanomaterial transfer in vivo were rich among immune cells, facilitating coordinated immune responses.

The effect of silica materials and their functionalization in the lipase catalyzed fat hydrolysis has been scarcely studied. Fifteen silica materials were prepared and their effect on the fat hydrolysis was measured, under simulated duodenal conditions, using the pH-stat method. The materials are composed of the combination of three supports (Stöber massive silica nanoparticles, Stöber mesoporous nanoparticles and UVM-7) and four surface functionalizations (methyl, trimethyl, propyl and octyl). In addition, the non-functionalized materials were tested. The functional groups were selected to offer a hydrophobic character to the material improving the interaction with the fat globules and the lipase. The materials are able to modulate the lipase activity and their effect depending on the support topology and the organic covering, being able to increase or reduce the fat hydrolysis. Depending of the material, relative fat hydrolysis rates of 75 to 140% in comparison with absence of the material were obtained. The results were analyzed by Partial Least Square Regression and suggest that the alkyl modified mesopores are able to improve the fat hydrolysis, by contrast the non-porous nanoparticles and the textural pores tend to induce inhibition. The effects are more pronounced for materials containing long alkyl chains and/or in absence of taurodeoxycholate.

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.

Nanoparticle-based drug delivery systems are among the most popular research topics in recent years. Compared with traditional drug carriers, mesoporous silica nanoparticles (MSN) offer modifiable surfaces, adjustable pore sizes and good biocompatibility. Nanoparticle-based drug delivery systems have become a research direction for many scientists. With the active target factionalized, scientists could deliver drug carriers into cancer cells successfully. However, drugs in cancer cells could elicit drug resistance and induce cell exocytosis. Thus, the drug cannot be delivered to its pharmacological location, such as the nucleus. Therefore, binding the cell membrane and the nuclear target on the nanomaterial so that the anticancer drug can be delivered to its pharmacological action site is our goal. In this study, MSN-EuGd was synthesized by doping Eu3+ and Gd3+ during the synthesis of MSN. The surface of the material was then connected to the TAT peptide as the nucleus target for targeting the cancer nucleus and then loaded with the anticancer drug camptothecin (CPT). Then, the surface of MSN-EuGd was bonded to the hyaluronic acid as an active target and gatekeeper. With this system, it is possible and desirable to achieve dual imaging and dual targeting, as well as to deliver drugs to the cell nucleus under a hyaluronidase-controlled release. The experimental approach is divided into three parts. First, we conferred the material with fluorescent and magnetic dual-imaging property by doping Eu3+ and Gd3+ into the MSN. Second, modification of the cell membrane target molecule and the nucleus target molecule occurred on the surface of the nanoparticle, making the nanoparticle a target drug carrier. Third, the loading of drug molecules into the carrier gave the entire carrier a specific target profile and enabled the ability to treat cancer. In this study, we investigated the basic properties of the drug carrier, including physical properties, chemical properties, and in vitro tests. The result showed that we have successfully designed a drug delivery system that recognizes normal cells and cancer cells and has good anticancer effects.

Mesoporous silica nanoparticles (MSN) have attracted a lot of attention during the past decade which is attributable to their versatile and high loading capacity, easy surface functionalization, excellent biocompatibility, and great physicochemical and thermal stability. In this review, we discuss the factors affecting the loading of protein into MSN and general strategies for targeted delivery and controlled release of proteins with MSN. Additionally, we also give an outlook for the remaining challenges in the clinical translation of protein-loaded MSNs.

Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd3+ complexes at very high loadings (15.5–28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety of methods including SEM and TEM, nitrogen adsorption measurements, thermogravimetric analysis (TGA), direct current plasma (DCP) spectroscopy, and powder X-ray diffraction (PXRD). The magnetic resonance (MR) relaxivities of these contrast agents were determined using a 3 T MR scanner. The r1 relaxivities of these nanoparticles range from 4.1 to 8.4 mM−1s−1 on a per Gd basis. Additionally, the MSN particles were functionalized with an organic fluorophore and cancer cell targeting peptide to allow for demonstration of both the optical and MR contrast enhancing capabilities in vitro.

Peroxidase mimetic catalytic atom transfer radical polymerization (ATRP) was first used to install tertiary amine-functionalized polymer brushes on the surface of mesoporous silica nanoparticles (MSNs) in a facile and highly efficient manner. Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brushes-grafted MSNs were fabricated by biocompatible deuterohemin-β-Ala-His-Thr-Val-Glu-Lys (DhHP-6)-catalyzed surface-initiated ATRP (SI-ATRP). The resulting organic–inorganic hybrid nanocarriers were fully characterized by Fourier transform-infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), SEM, TEM, Elemental analysis, Zeta-potential, and N2 adsorption–desorption isotherms, which demonstrated the successful coating of pH-responsive polymers on the MSN surface. Rhodamine 6G (Rh6G) dyes were further loaded within the mesopores of this nanocarrier, and the release of Rh6G out of MSNs in a controlled fashion was achieved upon lowing the solution pH. The electrostatic repulsion of positively-charged tertiary ammonium of PDMAEMAs in acidic environments induced the stretching out of polymer brushes on MSN surfaces, thus opening the gates to allow cargo diffusion out of the mesopores of MSNs.

The effect of silica materials and their functionalization in the lipase catalyzed fat hydrolysis has been scarcely studied. Fifteen silica materials were prepared and their effect on the fat hydrolysis was measured, under simulated duodenal conditions, using the pH-stat method. The materials are composed of the combination of three supports (Stöber massive silica nanoparticles, Stöber mesoporous nanoparticles and UVM-7) and four surface functionalizations (methyl, trimethyl, propyl and octyl). In addition, the non-functionalized materials were tested. The functional groups were selected to offer a hydrophobic character to the material improving the interaction with the fat globules and the lipase. The materials are able to modulate the lipase activity and their effect depending on the support topology and the organic covering, being able to increase or reduce the fat hydrolysis. Depending of the material, relative fat hydrolysis rates of 75 to 140% in comparison with absence of the material were obtained. The results were analyzed by Partial Least Square Regression and suggest that the alkyl modified mesopores are able to improve the fat hydrolysis, by contrast the non-porous nanoparticles and the textural pores tend to induce inhibition. The effects are more pronounced for materials containing long alkyl chains and/or in absence of taurodeoxycholate.

Mesoporous silica nanoparticles (MSN) have attracted a lot of attention during the past decade which is attributable to their versatile and high loading capacity, easy surface functionalization, excellent biocompatibility, and great physicochemical and thermal stability. In this review, we discuss the factors affecting the loading of protein into MSN and general strategies for targeted delivery and controlled release of proteins with MSN. Additionally, we also give an outlook for the remaining challenges in the clinical translation of protein-loaded MSNs.

Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd 3+ complexes at very high loadings (15.5-28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety of methods including SEM and TEM, nitrogen adsorption measurements, thermogravimetric analysis (TGA), direct current plasma (DCP) spectroscopy, and powder X-ray diffraction (PXRD). The magnetic resonance (MR) relaxivities of these contrast agents were determined using a 3 T MR scanner. The r 1 relaxivities of these nanoparticles range from 4.1 to 8.4 mM -1 s -1 on a per Gd basis. Additionally, the MSN particles were functionalized with an organic fluorophore and cancer cell targeting peptide to allow for demonstration of both the optical and MR contrast enhancing capabilities in vitro .

Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd 3+ complexes at very high loadings (15.5-28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety of methods including SEM and TEM, nitrogen adsorption measurements, thermogravimetric analysis (TGA), direct current plasma (DCP) spectroscopy, and powder X-ray diffraction (PXRD). The magnetic resonance (MR) relaxivities of these contrast agents were determined using a 3 T MR scanner. The r₁ relaxivities of these nanoparticles range from 4.1 to 8.4 mM -1 s -1 on a per Gd basis. Additionally, the MSN particles were functionalized with an organic fluorophore and cancer cell targeting peptide to allow for demonstration of both the optical and MR contrast enhancing capabilities in vitro.