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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

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., Confined growth of ZIF-8 nanocrystals in the large mesopores of organosilica nanoparticles with tetrasulfide bond is reported to upregulate mRNA translation and enhance delivery performance.

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.

International audience; (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.