Search

Nano-controlled release formulations present a promising strategy to mitigate pesticide losses and enhance efficiency. In this study, a pH and GSH-responsive nanoplatform using mesoporous organosilica nanoparticles (MONs) as a carrier and poly(tannic acid) (PTA) as capping agent was established for controlling prochloraz (Pro) release. The obtained Pro@MON@PTA was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA). The results indicate the successful preparation of Pro@MON@PTA nanoparticles, featuring uniform particle size (190 nm), excellent dispersibility, and a prochloraz loading efficiency of 17.2%. Evaluation of contact angle and adhesion work demonstrated superior adhesion of MON@PTA to rice leaves compared to MON. Controlled release studies revealed dual-responsive release properties of Pro@MON@PTA to acid and GSH. Additionally, photostability testing indicated effective ultraviolet light shielding by the carrier, reducing prochloraz degradation under irradiation. Bioassay results indicated equivalent fungicidal activity against Magnaporthe oryzae between Pro@MON@PTA and prochloraz technical and prochloraz EW after a 7-day treatment. However, in vivo experiments demonstrated that Pro@MON@PTA exhibited superior control efficacy compared to prochloraz EW. These findings suggested that MON@PTA holds significant potential for plant disease management. [ABSTRACT FROM AUTHOR]

Metal ion‐based inhibition of urease activity is a promising strategy for treating Helicobacter pylori (H. pylori) infections. However, the challenges of safe delivery and reducing cytotoxicity persist. In this study, an innovative nanocarrier capable of acid‐responsive release of Ag+ and antibiotics is developed, with complete degradation after treatment. Mesoporous organosilica nanoparticle (MON) is encapsulated with hyaluronic acid (HA) to prevent drug leakage and further coated with bacterial outer membrane vesicle (OMV) from Escherichia coli Nissle 1917, creating a nanocarrier with cell‐protective capabilities. Ag+ and antibiotic clarithromycin (CLR) are incorporated into the nanocarrier to form CLR‐Ag+@MON@HA@OMV (CAMO), designed for the targeted treatment of gastric H. pylori infection. The HA encapsulation ensures acid‐responsive release of CLR and Ag+ in the stomach, preventing premature release at non‐inflammatory sites. There is a potential for Ag⁺ in CAMO to replace Ni2⁺ at the active site of urease, enhancing the bactericidal effect of CLR through urease inhibition. Furthermore, the OMV provides additional cytoprotection, mitigating cell damage and inflammation response induced by the H. pylori infection. This study introduces a safe and effective nanocarrier that eradicates H. pylori and alleviates gastric inflammation. [ABSTRACT FROM AUTHOR]

Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H 2 O 2 present in infected tissues into O 2 , alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirmed that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform. This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies. [Display omitted] [ABSTRACT FROM AUTHOR]

Haijun Li,1,* Dongbei Li,2,* Fangman Chen,3 Chao Yang,3 Xiaogai Li,1 Yuan Zhang,1 Chunlan Hua,1 Xiaoxu Ma,1 Xin Zhao,1 Dan Shao,3 Yingshuai Wang,4 Liang Ming1 1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, 450000, People’s Republic of China; 3Institutes for Life Sciences, School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510630, People’s Republic of China; 4School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingshuai WangSchool of Life Science and Technology, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of ChinaEmail yingshuaiwang1987@163.comLiang MingDepartment of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaEmail mingliang3072@163.comPurpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria.Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 μg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values.Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.Keywords: mesoporous organosilica nanoparticles, nanosilver, gentamicin, GSH-responsive release, antibiotics-resistant bacteria

Abstract Biodegradation is a crucial issue for silica‐based mesoporous nanoparticles that is related to the biosafety in tumor therapy. Nowadays, mesoporous silica nanoparticles (MSNs) have been intensively developed to construct multifunctional nanosystems for tumor therapy due to their biocompatibility, high drug loading capacity and easy functionalization; however, their biodegradation is relatively slow and still under debate. To improve the biodegradability of silica‐based mesoporous nanoparticles, a simple organic‐inorganic hybridization strategy to synthesize mesoporous organosilica nanoparticles (MONs) has been successfully developed. By hybridizing the silica framework (–Si–O–Si–) with stimuli‐sensitive organic moieties to form organic‐inorganic network (–Si–R–Si–, R: organic moiety), when exposed to the stimuli environment, the breakdown of the organic‐inorganic network could accelerate the degradation of MONs, which is great promising for MONs as a multifunctional therapeutic nanoplatform in tumor therapy. This review aims to summarize the degradation strategies for MONs to improve biodegradability in recent years, and highlight the potential applications of MONs in tumor therapy. Finally, we also discuss the challenges of MONs for tumor therapy in future clinical translation.

Biodegradation is a crucial issue for silica‐based mesoporous nanoparticles that is related to the biosafety in tumor therapy. Nowadays, mesoporous silica nanoparticles (MSNs) have been intensively developed to construct multifunctional nanosystems for tumor therapy due to their biocompatibility, high drug loading capacity and easy functionalization; however, their biodegradation is relatively slow and still under debate. To improve the biodegradability of silica‐based mesoporous nanoparticles, a simple organic‐inorganic hybridization strategy to synthesize mesoporous organosilica nanoparticles (MONs) has been successfully developed. By hybridizing the silica framework (–Si–O–Si–) with stimuli‐sensitive organic moieties to form organic‐inorganic network (–Si–R–Si–, R: organic moiety), when exposed to the stimuli environment, the breakdown of the organic‐inorganic network could accelerate the degradation of MONs, which is great promising for MONs as a multifunctional therapeutic nanoplatform in tumor therapy. This review aims to summarize the degradation strategies for MONs to improve biodegradability in recent years, and highlight the potential applications of MONs in tumor therapy. Finally, we also discuss the challenges of MONs for tumor therapy in future clinical translation. [ABSTRACT FROM AUTHOR]

Zeolitic imidazolate framework-8 (ZIF-8) and its composites have diverse applications. However, ZIF-8-based nanocomposites are mainly used as carriers in biomolecular delivery, with the functions of metal ions and ligands rarely used to modulate the biofunctions. In this work, dendritic mesoporous organosilica nanoparticles (DMONs) with tetrasulfide bond were used to confine ZIF-8 growth partially inside mesopores as a novel nanocomposite for mRNA delivery. Each component in the resultant DMONs-ZIF-8 contributed to mRNA delivery applications, including high loading benefitting from positively charged ZIF-8 and large mesopores of DMONs, endosomal escape promoted by the imidazole ring of ZIF-8, and long-term glutathione depletion mediated by both zinc ions and tetrasulfide bond. Combined together, DMONs-ZIF-8 demonstrated enhanced mRNA translation and better transfection efficiency than commercial products and toxic polymer-modified DMONs in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The recent focus of cancer therapeutics research revolves around modulating the immunosuppressive tumor microenvironment (TME) to enhance efficacy. The tumor stroma, primarily composed of cancer-associated fibroblasts (CAFs), poses significant obstacles to therapeutic penetration, influencing resistance and tumor progression. Reprogramming CAFs into an inactivated state has emerged as a promising strategy, necessitating innovative approaches. This study pioneers the design of a nanoformulation using pioglitazone, a Food and Drug Administration-approved anti-diabetic drug, to reprogram CAFs in the breast cancer TME. Glutathione (GSH)-responsive dendritic mesoporous organosilica nanoparticles loaded with pioglitazone (DMON-P) are designed for the delivery of cargo to the GSH-rich cytosol of CAFs. DMON-P facilitates pioglitazone-mediated CAF reprogramming, enhancing the penetration of doxorubicin (Dox), a therapeutic drug. Treatment with DMON-P results in the downregulation of CAF biomarkers and inhibits tumor growth through the effective delivery of Dox. This innovative approach holds promise as an alternative strategy for enhancing therapeutic outcomes in CAF-abundant tumors, particularly in breast cancer.

The interdisciplinary integration among material science, nanotechnology and biology has been promoting the emergences of a large number of feasible nanoplatforms for diverse biomedical applications. Thanks to the unique mesoporous structure, large specific surface area, abundant surface chemistry and tunable framework composition, mesoporous silica nanoparticles (MSNs) and mesoporous organosilica nanoparticles (MONs) have been extensively applied for diverse therapeutic, or diagnostic applications. The past two decades have witnessed the blooming growth of researches on the elaborate design and fabrication of multifunctional MSNs/MONs-based nanosystems, which have greatly pushed forward the development of next-generation theranostic biomaterials. These mesoporous silica-based nanomaterials feature varied structural, compositional and morphological characteristics, leading to the great diversity in their downstream physicochemical properties and theranostic performances, which further catalyzes the emergence of advanced therapeutic strategies for optimized treatment efficacies and mitigated side effects. In this review, we will comprehensively elucidate very-recent advances on the construction of MSNs/MONs-based theranostic nanoplatforms for various therapeutic and diagnostic applications, and discuss the underlying material chemistry of these exquisite nanosystems that confers varied theranostic functionalities. Especially, the interdependent relationship among the synthesis, biological effects and biomedical applications of MSNs and MONs will be discussed in depth, and their further clinical-translation potential/challenge will be clarified and outlooked. It is highly expected that we will witness a second leap-forward development of the biomedical applications of MSNs and MONs in the next one or two decades, especially for the further clinical translation. [ABSTRACT FROM AUTHOR]

In the work, yolk–shell structured mesoporous organosilica nanoparticles (YSMONs) are successfully prepared by a mild alkalescent etching approach. The method is very convenient, in which mesostructured organosilica nanospheres are directly transformed into yolk–shell structures after etching with mild alkalescent solution (e.g. sodium carbonate solution). The prepared YSMONs have ethane-bridged frameworks, a monodisperse diameter (320 nm), a large pore volume (1.0 cm 3  g −1 ), a uniform mesopore (2.4 nm) and a high surface area (1327 m 2  g −1 ). In vitro cytotoxicity and hemolysis assays demonstrate the ethane-bridged YSMONs possess excellent biocompatibility and low hemolysis activity. In addition, the YSMONs show a high loading capacity up to 181 μg mg −1 for anti-cancer drug doxorubicin (DOX). Confocal laser scanning microscopy and flow cytometry analyses show that the DOX loaded YSMONs (YSMONs-DOX) can be effiectively internalized by multidurg resistant MCF-7/MDR human breast cancer cells. The chemotherapy against MCF-7/MDR cells demonstrate that the YSMONs-DOX possess higher therapeutic efficacy compared to that of free DOX, suggesting that the YSMONs synthesized by the mild alkalescent etching method have great promise as advanced nanoplatforms for biological applications. [ABSTRACT FROM AUTHOR]

Gemcitabine hydrochloride is an FDA-approved chemotherapeutic drug used in the treatment of various cancers. Several drawbacks of gemcitabine, including its short in vivo half-life of 8-17 min associated with a rapid excretion by the kidneys and its poor membrane permeability, have inspired research on a nanodelivery approach. In this study, we report ethylene-based periodic mesoporous organosilica nanoparticles (PMOs) for photodynamic therapy and the autonomous delivery of gemcitabine in cancer cells. Porphyrins were used as photosensitizers and were localized in the walls of the PMOs while a high loading capacity of gemcitabine was observed in the porous structure. Depending on the nature of the photosensitizer, and its aggregation state, we were able to perform one or two-photon photodynamic therapy. Two-photon excited photodynamic therapy combined with gemcitabine delivery led to a synergy and a very efficient cancer cell killing. [ABSTRACT FROM AUTHOR]

In this work, we report a facile biphasic-to-monophasic successive co-assembly approach to synthesize yolk–shell structured mesoporous organosilica nanoparticles (MONs). The yolk–shell structured MONs possess ethane-bridged frameworks, high surface area (1023 m 2 g −1 ), radially oriented mesochannels (3.8 nm), large pore volume (0.99 cm 3 g −1 ), and tunable diameter (147–324 nm) and shell thickness (23–53 nm). The biphasic-to-monophasic successive co-assembly method is intrinsically simple and requires neither sacrificial templates nor multistep coating processes. The key of the method is that the interiors of the mesostructured organosilica nanospheres grown in the biphasic system have a lower condensation degree and Si-C-C-Si species content than the outer shells formed in the monophasic system. Thus, the interior layer is attracted by OH −1 anions and dissolved in the monophasic system, forming the yolk–shell structures. In vitro cytotoxicity and haemolysis assays demonstrate that the ethane-bridged yolk–shell MONs possess excellent biocompatibility. Furthermore, the chemotherapy drug doxorubicin (DOX) is loaded into the yolk–shell MONs to kill drug-resistant MCF-7/ADR human breast cancer cells. Compared with free DOX and DOX-loaded typical MONs, the DOX-loaded yolk–shell MONs have higher chemotherapeutic efficacy against MCF-7/ADR cells, suggesting the great potential of yolk–shell MONs synthesized via the biphasic-to-monophasic successive co-assembly approach in the biomedical field. [ABSTRACT FROM AUTHOR]

(1) Background: Nanomedicine has recently emerged as a new area of research, particularly to fight cancer. In this field, we were interested in the vectorization of pepstatin A, a peptide which does not cross cell membranes, but which is a potent inhibitor of cathepsin D, an aspartic protease particularly overexpressed in breast cancer. (2) Methods: We studied two kinds of nanoparticles. For pepstatin A delivery, mesoporous silica nanoparticles with large pores (LPMSNs) and hollow organosilica nanoparticles (HOSNPs) obtained through the sol–gel procedure were used. The nanoparticles were loaded with pepstatin A, and then the nanoparticles were incubated with cancer cells. (3) Results: LPMSNs were monodisperse with 100 nm diameter. HOSNPs were more polydisperse with diameters below 100 nm. Good loading capacities were obtained for both types of nanoparticles. The nanoparticles were endocytosed in cancer cells, and HOSNPs led to the best results for cancer cell killing. (4) Conclusions: Mesoporous silica-based nanoparticles with large pores or cavities are promising for nanomedicine applications with peptides.

Foot-and-mouth disease (FMD), a serious, fast-spreading, and virulent disease, has led to huge economic losses to people all over the world. Vaccines are the most effective way to control FMD. However, the weak immunogenicity of inactivated FMD virus (FMDV) requires the addition of adjuvants to enhance the immune effectiveness of the vaccines. Herein, we formulated and fabricated biodegradable dendritic mesoporous tetrasulfide-doped organosilica nanoparticles SOMSN with imiquimod complex (SOMSN-IMQ) and used it as a platform for FMD vaccine delivery and as an adjuvant. SOMSN-IMQ demonstrated excellent stability for 6 months when stored in PBS, while it could be completely degraded within 42 days in SBF at room temperature. Biosafety experiments such as cell toxicity, hemolysis, and histology indicated that the as-prepared SOMSN-IMQ showed nontoxicity and good biocompatibility. Furthermore, SOMSN-IMQ exhibited a maximum adsorption capacity of 1000 μg/mg for inactivated FMDV antigens. Our results showed that SOMSN-IMQ can be effectively engulfed by RAW264.7 cells in a dose-dependent manner. After immunization, SOMSN-IMQ@FMDV can elicit persistent higher antibody levels, higher IgG2a/IgG1 ratio, and cytokine expression, which indicated that SOMSN-IMQ@FMDV triggered superior humoral and cellular immune responses. Moreover, SOMSN-IMQ could provoke maturation and activation of dendritic cells in lymph nodes (LDCs) as well as the proliferation of lymphocytes in vivo . Thus, SOMSN-IMQ could promote effective and potent immunity and provide a promising adjuvant platform for FMDV vaccination with acceptable safety.

Citronellol (CI)-loaded, chitosan (CS)-enclosed dendritic mesoporous organosilica nanoparticles (CI@D-MONs@CS) are successfully fabricated. The synthesized CI@D-MONs@CS present spherical shape with the particle size of 424±24 nm in diameter and dendritic mesopores. CI loading ratio of CI@D-MONs@CS is about 12.42% from TGA analysis. CI release from CI@D-MONs@CS exhibits pH-redox dual responsiveness. More interesting, the axillary deodorant effect is investigated with Staphylococcus haemolyticus in an artificial sweat model. The results show that CI@D-MONs@CS present an excellent bacteria-killing effect and the smell of artificial sweat is greatly improved, avoiding the formation of undesirable odorant compounds from the bacteria. The obtained CI@D-MONs@CS is a potential carrier of natural fragrance or actives with dual responsive release. The application of CI@D-MONs@CS is a new and effective strategy to the axillary odor problem. • The pH-redox dual responsive nanoparticles CI@D-MONs@CS were designed and fabricated. • Chitosan formed the pH-responsive "gate" of CI@D-MONs@CS. • CI@D-MONs@CS exhibited significantly enhanced and durable antibacterial capacities. • CI@D-MONs@CS greatly reduced the off-odor caused by the axillary bacteria. • Application of CI@D-MONs@CS was a new and effective strategy to the axillary odor problem. [ABSTRACT FROM AUTHOR]

[Display omitted] • Magnetic resonance technique for temperature-controlled ultrasound irradiation. • Hollow-dendritic-silica-nanoparticles-based smart drug carriers. • Concurrent surfactant removal and α-FeOOH species loading via Fenton reaction. • L-menthol as thermal-sensitive "Flowing Valve" rendering stepwise drug release. • Visualized drug release via magnetic resonance imaging. Focused ultrasound (FUS) controlled drug delivery is maturing towards a highly precise and intelligent approach via the integration of ultrasound-responsive nanocarriers and the state-of-the-art magnetic resonance (MR) technique. Herein, an ultrasound-responsive nanoplatform (Dox@L@FeHD) is developed based on hollow dendritic mesoporous organosilica nanoparticles (HDMONs). Using a facile Fenton reaction, ultrasmall α-FeOOH species are anchored within HDMONs, followed by implanting both doxorubicin (Dox) and L-menthol (LM) to obtain Dox@L@FeHD, which shows a T 1 -T 2 bimodal MR contrast feature. Under mild hyperthermia condition (45 °C), the encapsulated LM undergoes a phase-transition and redistribution ("flowing") within HDMONs, resulting in a rearranged pore structure of Dox@L@FeHD post stimulation. Consequently, Dox shifts from burst release to sustained release, as visualized by MR imaging due to the altered MR contrast feature of Dox@L@FeHD concurrently. In vivo FUS stimulation of Dox@L@FeHD is executed using a self-developed feedback temperature control algorithm to render a constant temperature of 45 °C at the targeted tumor region, thus triggering the in-situ stepwise Dox release, which induces effective retardation of tumor growth. This work demonstrates an elaborate marriage of smart mesoporous nanocarriers and the MR-FUS technique for the accurate regulation of drug release kinetics. [ABSTRACT FROM AUTHOR]

• In-depth introduction of dendritic mesoporous organosilica nanoparticles (DMONs). • The synthetic techniques and mechanisms of DMONs. • The construction strategies to DMONs-based particular architectures. • Current challenges of this novel nanomaterial for future desired applications. • Future prospects and developments of DMONs-related subject. [Display omitted] Dendritic mesoporous organosilica nanoparticles (DMONs) possess three-dimensional (3D) center-radial nanochannels and hierarchical nanopores, which endows themselves with unique structural features and larger pore volumes, more open pore channels, more accessible internal spaces, etc., compared to conventional mesoporous organosilica nanoparticles (MONs). In addition, organic moieties in DMONs skeleton bring about novel biocompatibility, hydrophobicity, and biodegradability, greatly superior to pure inorganic dendritic mesoporous silica nanoparticles (DMSNs) in terms of biochemical applications. Diverse guest species (such as drugs, proteins, or RNA) could be easily loaded onto chemically active sites of the channels' interfaces, achieving their efficient transportation and the subsequent delivery. During the last five years, DMONs have attracted certain degree of attention and experienced non-ignorable development. Therefore, it is necessary and urgent to popularize this brand-new DMONs. To the best of our knowledge, no document has been reported with special focus on its recent progress. For the first time, this comprehensive review provides a critical survey on the synthetic techniques and the corresponding mechanisms of DMONs, DMONs-based particular architectures (like the hollow, core-shell, multi-shelled, etc.), as well as their application domains. Biochemically related applications are emphatically analyzed in the aspects of the design thoughts, manufacturing processes, integrated functionalities, and action mechanisms. It is sincerely expected that this summary and in-depth discussion could give materials scientists and biochemists certain inspiration to accelerate DMONs subject's booming evolution. [ABSTRACT FROM AUTHOR]

Designing a transformable nanosystem with improved tumor accumulation and penetration by tuning multiple physicochemical properties remains a challenge. Here, a near-infrared (NIR) light-driven nanosystem with size and charge dual-transformation for deep tumor penetration is developed. Methods: The core-shell nanotransformer is realized by integrating diselenide-bridged mesoporous organosilica nanoparticles as a reactive oxygen species (ROS)-responsive core with an indocyanine green (ICG)-hybrid N-isopropyl acrylamide layer as a thermosensitive shell. After loading doxorubicin (DOX), negatively charged nanomedicine prevents DOX leakage, rendering prolonged blood circulation time and high tumor accumulation. Results: Upon NIR light irradiation, mild photothermal effects facilitate the dissociation of the thermosensitive shell to achieve negative-to-positive charge reversal. Meanwhile, ICG-generated ROS cleave the diselenide bond of the organosilica core, resulting in rapid matrix degradation that produces DOX-containing smaller fragments. Such a light-driven dual-transformable nanomedicine simultaneously promotes deep tumor penetration and implements sufficient chemotherapy, along with evoking robust immunogenic cell death effects in vitro and in vivo . With the combination of a programmed cell death protein-1 (PD-1) checkpoint blockade, the nanotransformer remarkably blocks primary tumor growth and pulmonary metastasis of breast cancer with low systemic toxicity. Conclusions: This study develops a promising strategy to realize high tumor accumulation and deep penetration of light-transformable nanomedicine for efficient and safe chemo-immunotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Despite the advantages of mesoporous silica nanoparticles (MSNs) in drug delivery, the inherent non-biodegradability seriously impedes the clinical translation of inorganic MSNs, so the current research focus has been turned to mesoporous organosilica nanoparticles (MONs) with higher biocompatibility and easier biodegradability. Recent remarkable advances in silica fabrication chemistry have catalyzed the emergence of a library of MONs with various structures and functions. This review will summarize the latest state-of-the-art studies on the precise control of morphology, structure, framework, particle size and pore size of MONs, which enables the precise synthesis of MONs with suitable engineering for precision stimuli-responsive drug delivery/release, bioimaging and synergistic therapy. Besides, the potential challenges about the future development of MONs are also outlooked with the intention of attracting more researchers to promote the clinical translation of MONs. [ABSTRACT FROM AUTHOR]

• Overview of the organosilica nanoparticles application on cancer drug delivery. • Practical approaches for developing stimuli-responsive drug release are described. • Review of the organosilica nanoparticles biocompatibility. The application of nanomaterials is regarded nowadays as a highly promising approach for overcoming the limitations of the currently available cancer treatments, contributing for the creation of more effective, precise, and safer therapies. In the last years, organosilica nanoparticles arisen as alternatives to the most common mesoporous silica nanoparticles. The organosilica nanoparticles combine the advantages of the mesoporous silica, such as structural stability and mesoporous structure, with the increased biocompatibility and biodegradability of organic materials. Therefore, the variety of organic bridges that can be incorporated into the silica matrix allowed the development of new and exciting compositions, properties, and functions for improving the therapeutic effectiveness of the anticancer nanomedicines. In this review, the strategies that have been explored to create stimuli-responsive organosilica-based drug delivery systems are highlighted, describing the practical approaches and mechanisms controlling the drug release. Additionally, the organosilica nanoparticles surface modifications aimed for increasing the blood circulation time and the tumor targeting are also described. [ABSTRACT FROM AUTHOR]

• Biodegradable mesoporous organosilica nanoparticles are fabricated via a one-pot synthesis. • Chlorhexidine (CHX) is selected as a cationic template to form the mesoporous structure. • CHX@MONs exhibit GSH-triggered CHX release manner. • CHX@MONs exhibit comparable antibacterial effects with free CHX. • CHX@MONs exhibit less cytotoxicity than free CHX. Chlorhexidine (CHX) is a widely used antiseptic in various infection control practices. In this work, we have developed biodegradable mesoporous organosilica nanoparticles (MONs) through a one-pot synthesis by employing CHX as a bifunctional agent that not any acts as a cationic template to form the structure of mesopores but also serves as a broad-spectrum antiseptic. The resulting CHX@MONs exhibit a relatively high CHX content and glutathione (GSH)-responsive release of CHX via a matrix-degradation-controlled mechanism, leading to comparable antibacterial effects with CHX on both Escherichia coli and Staphylococcus aureus. Furthermore, the effective antibacterial concentration of CHX@MONs shows less cytotoxicity toward normal cells. Our findings will help increase the use of CHX as an antiseptic agent, especially for responsive drug release upon bacterial infection. [ABSTRACT FROM AUTHOR]

Amplifying the chemotherapy-driven immunogenic cell death (ICD) for efficient and safe cancer chemoimmunotherapy remains a challenge. Here, a potential ICD nanoamplifier containing diselenide-bridged mesoporous organosilica nanoparticles (MONs) and chemotherapeutic ruthenium compound (KP1339) to achieve cancer chemoimmunotherapy is tailored. KP1339-loaded MONs show controlled drug release profiles via glutathione (GSH)-responsive competitive coordination and matrix degradation. High concentration of MONs selectively evoked reactive oxygen species production, GSH depletion, and endoplasmic reticulum stress in cancer cells, thus amplifying the ICD of KP1339 and boosting robust antitumor immunological responses. After the combination of PD-L1 checkpoint blockade, cancer cell membrane-cloaked KP1339-loaded MONs not only regress primary tumor growth with low systemic toxicity, but also inhibit distant tumor growth and pulmonary metastasis of breast cancer. The results have shown the potential of coordination and redox dual-responsive MONs boosting amplified ICD for cancer chemoimmunotherapy., (© 2021 Wiley-VCH GmbH.)

Transcatheter arterial chemoembolization (TACE) is standard locoregional therapy for hepatocellular carcinoma (HCC) that involves the injection of chemotherapeutic drugs with embolic agents into tumor tissues through intra-arterial transcatheter infusion. TACE technology using lipiodol emulsion has been most widely used in the treatment of human HCC. However, lipiodol emulsions with anticancer drugs do not stably maintain high drug concentrations at tumor sites. Herein, we developed a dual-modality imaging nanoplatform for the TACE treatment of liver cancer by integrating periodic mesoporous organosilica (PMO) with magnetite (Fe 3 O 4 ) nanoparticles and Cy5.5 molecules (denoted as Fe 3 O 4 @PMO-Cy5.5). Fe 3 O 4 @PMO-Cy5.5 showed an excellent doxorubicin (Dox)-loading capacity, sensitive drug release behavior under acidic conditions, and good biocompatibility. Moreover, Cy5.5-mediated optical imaging showed that Dox-loaded Fe 3 O 4 @PMO-Cy5.5 (Fe 3 O 4 @PMO-Cy5.5-Dox) could enter liver cancer cells and effectively inhibit their growth. In addition, Fe 3 O 4 @PMO-Cy5.5-Dox was used in combination with transarterial embolization for the treatment of in situ VX2 liver tumors in rabbits. Magnetic resonance imaging (MRI) evaluation showed that Fe 3 O 4 @PMO-Cy5.5-Dox perfused through arteries was deposited into liver tumors, and Fe 3 O 4 @PMO-Cy5.5-Dox combined with lipiodol to control liver tumors yielded the optimal therapeutic effect. In addition, histological analysis showed that compared with both lipiodol embolization and traditional lipiodol combined with Dox chemoembolization, Fe 3 O 4 @PMO-Cy5.5-Dox combined with lipiodol chemoembolization induced more complete tumor tissue necrosis. In summary, these results indicate that the Fe 3 O 4 @PMO-Cy5.5-Dox platform has the potential to become an advanced tool for the transarterial treatment of unresectable liver cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Zeolitic imidazolate framework-8 (ZIF-8) and its composites have diverse applications. However, ZIF-8-based nanocomposites are mainly used as carriers in biomolecular delivery, with the functions of metal ions and ligands rarely used to modulate the biofunctions. In this work, dendritic mesoporous organosilica nanoparticles (DMONs) with tetrasulfide bond were used to confine ZIF-8 growth partially inside mesopores as a novel nanocomposite for mRNA delivery. Each component in the resultant DMONs-ZIF-8 contributed to mRNA delivery applications, including high loading benefitting from positively charged ZIF-8 and large mesopores of DMONs, endosomal escape promoted by the imidazole ring of ZIF-8, and long-term glutathione depletion mediated by both zinc ions and tetrasulfide bond. Combined together, DMONs-ZIF-8 demonstrated enhanced mRNA translation and better transfection efficiency than commercial products and toxic polymer-modified DMONs in vitro and in vivo ., (© The Author(s) 2020. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

(1) Background: Nanomedicine has recently emerged as a new area of research, particularly to fight cancer. In this field, we were interested in the vectorization of pepstatin A, a peptide which does not cross cell membranes, but which is a potent inhibitor of cathepsin D, an aspartic protease particularly overexpressed in breast cancer. (2) Methods: We studied two kinds of nanoparticles. For pepstatin A delivery, mesoporous silica nanoparticles with large pores (LPMSNs) and hollow organosilica nanoparticles (HOSNPs) obtained through the sol–gel procedure were used. The nanoparticles were loaded with pepstatin A, and then the nanoparticles were incubated with cancer cells. (3) Results: LPMSNs were monodisperse with 100 nm diameter. HOSNPs were more polydisperse with diameters below 100 nm. Good loading capacities were obtained for both types of nanoparticles. The nanoparticles were endocytosed in cancer cells, and HOSNPs led to the best results for cancer cell killing. (4) Conclusions: Mesoporous silica-based nanoparticles with large pores or cavities are promising for nanomedicine applications with peptides. [ABSTRACT FROM AUTHOR]

High intensity focused ultrasound (HIFU) surgery generally suffers from poor precision and low efficiency in clinical application, especially for cancer therapy. Herein, a multiscale hybrid catalytic nanoreactor (catalase@MONs, abbreviated as C@M) has been developed as a tumor-sensitive contrast and synergistic agent (C&SA) for ultrasound-guided HIFU cancer surgery, by integrating dendritic-structured mesoporous organosilica nanoparticles (MONs) and catalase immobilized in the large open pore channels of MONs. Such a hybrid nanoreactor exhibited sensitive catalytic activity toward H 2 O 2 , facilitating the continuous O 2 gas generation in a relatively mild manner even if incubated with 10 μM H 2 O 2 , which finally led to enhanced ablation in the tissue-mimicking PAA gel model after HIFU exposure mainly resulting from intensified cavitation effect. The C@M nanoparticles could be accumulated within the H 2 O 2 -enriched tumor region through enhanced permeability and retention effect, enabling durable contrast enhancement of ultrasound imaging, and highly efficient tumor ablation under relatively low power of HIFU exposure in vivo. Very different from the traditional perfluorocarbon-based C&SA, such an on-demand catalytic nanoreactor could realize the accurate positioning of tumor without HIFU prestimulation and efficient HIFU ablation with a much safer power output, which is highly desired in clinical HIFU application.

Enhancing the tumor-targeting delivery of chemotherapeutic drugs is important yet challenging for improving therapeutic efficacy and reducing the side effects. Here, we first construct a drug delivery system for targeting tumor acidic microenvironment by modification of pH (low) insertion peptide (pHLIP) on mesoporous organosilica nanoparticles (MONs). The MONs has thioether-bridged framework, uniform diameter (60 nm), good biocompatibility, and high doxorubicin (DOX) loading capacity (334 mg/g). The DOX loaded in the pHLIP modified MONs can be released responsive to glutathione and low pH circumstance, ensuring the chemotherapeutic drug exerts higher cytotoxic effects to cancer cells than normal cells because of high intracellular GSH of tumor cells and low pH of tumor microenvironment. Moreover, the engineered MONs exhibit higher cellular uptake in pH 6.5 medium by MDA-MB-231 and MCF-7 cells than the particles decorated with polyethylene glycol (PEG). Importantly, the pHLIP-mosaic MONs with DOX displays better cytotoxic effects against the breast cancer cells in pH 6.5 medium than pH 7.4 medium. The in vivo experiments demonstrate that the pHLIP modified MONs are accumulated in the orthotopic breast cancer via targeting to acidic tumor microenvironment while no serious pathogenic effects was observed. After loading DOX, the pHLIP-modified MONs display better therapeutic effects than the control groups on the growth of MCF-7 breast cancers, showing promise for enhancing chemotherapy.

Large pore (4.6-7.6 nm) and well-dispersed benzene bridged mesoporous organosilica nanoparticles with uniform particle size of ≈50 nm are prepared via a biphasic approach. They can be directly used as nanocarriers without surface modification for the intracellular delivery of therapeutic proteins., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)