Mesoporous Silica Nanoparticles Drug Deliery System Applied In Tumor Therapy And SARS-CoV-2 Vaccine Development

Mesoporous silica nanoparticles(MSNs)have become good carriers of drug mol-ecules due to their good biocompatibility,large specific surface area,adjustable particle size/pore size,controllable morphology and ordered structure.In this paper,we fouced on the application of MSNs as the drug delivery carrier in tumor therapy and develop-ment of novel coronavirus vaccine.(1)Targeted tumor therapy with CAIX modified mesoporous silica nanoparticles.Based on the fact that carbonic anhydrase IX(CAIX)is not expressed in normal tissues,but highly expressed in various solid tumors,we have constructed a tumor targeted drug delivery system“MSNs-CAIX”using CAIX antibody as a targeting ligand.After anti-cancer model drug doxorubicin hydrochloride(DOX)was loaded,CAIX was grafted onto DOX@MSNs surface with disulfide bond by multi-step chemical reaction.In the reduction of glutathione(GSH),the drug redox-responsive release was achieved owing to the cleavage of the disulfide bond.In vitro,remarkably more DOX@MSNs-CAIX was internalized into CAIX positive 4T1 cells(mouse breast cancer cells)by receptor-mediation.The in vivo stuies further demonstrated more DOX@MSNs-CAIX accumu-lated in breast cancer tumors,significantly improving the targeted anti-tumor therapeu-tic effect.(2)Construction of ZnO gated p H-responsive biodegradable mesoporous silica nanodrug delivery system.Traditional MSNs drug delivery system suffer from bioac-cumulation in vivo and premature drug release due to low degradation rate and lack of protective gatekeeper.DOX@BMSNs-ZnO,a kind of biodegradable,p H-responsive drug delivery system,was constructed using BMSNs as the carrier,DOX as the model drug and ZnO quantum dots as the blocking agent.Acidic degradable MSCNs were successfully synthesized by doping Ca²⁺and PO₄^3-into the MSNs'framework.ZnO was successfully block DOX@BMSNs by amide bond.DOX was hardly released under neutral conditions,and p H-responsive release was achieved with the dissolution of ZnO under acidic conditions.Cytotoxicity and endocytosis experiments showed that BMSNs-ZnO could effectively transport DOX into cells to inhibit the growth of tumor cells.(3)Study on mesoporous silica nanoparticles as a novel severe acute respiratory syndrome coronavirus-2(SARS-Co V-2)peptides vaccine carrier.Nano-vaccine B/T@BMSNs were prepared by loading B-and T-cell epitopes of SARS-Co V-2-S pro-tein into BMSNs.Two antigens loaded particles(B2@BMSNs and T3@BMSNs)were selected to observe the endocytosis in Raw264.7.The biological safety of B/T@BMSNs was evaluated in mice.The effects of B/T@BMSNs on the body weight and life status of mice were observed and the histocompatibility of BMSNs was ana-lyzed by histopathological section.The immune response of mice induced by B/T@BMSNs was detected by enzyme-linked immunosorbent assay(ELISA).The re-sults showed that B/T@BMSNs has good biocompatibility and could effectively induce humoral and cellular immunity,which would be a safe and effective candidate vaccine.This paper includes 111 figures,13 tables and 216 references.