Construction And Anti-tumor Effect Of Metal Engineered Mesoporous Silica Drug Delivery System

At present,the number of cancer cases is increasing,and the traditional cancer treatment methods have great limitations,so there is an urgent need to develop efficient and precise new cancer treatment methods.The rapid development of nanomedicine provides a new idea for cancer treatment.the use of nano-carriers to deliver drugs can improve the therapeutic effect and reduce toxic side effects.Mesoporous silica nanoparticles integrated with the advantages of both inorganic materials and mesoporous materials are highly promising in the field of nano drug delivery.Therefore,in this dissertation,mesoporous silica nanoparticles were used as carriers,which were endowed with additional functionalities through metal engineering.Subsequently,the carriers were loaded with chemotherapeutic drugs for tumor synergistic therapy.The main contents and conclusions are as follows:（1）Calcium-doped mesoporous organosilica nanoparticles（BT-Ca-MSN）were successfully synthesized by a sol-gel method and an acetone extraction method.The nano-carriers showed a uniform spherical morphology with an average diameter of about 30 nm and pore size of 3.85nm.The loading content of BT-Ca-MSN on adriamycin hydrochloride（Dox）was calculated to be 11.89%by high performance liquid chromatography.The biodegradation behavior of the carrier was further investigated,and the carrier was degraded completely within one day under acidic and reducing conditions.The in-vitro cytotoxicity test showed that the nano-carrier could effectively kill tumor cells without obvious toxicity to normal cells.Furthermore,BT-Ca-MSN could synergize with the loaded Dox to inhibit tumor cell proliferation,significantly enhancing the anti-cancer effect.（2）Calcium-and iron-doped mesoporous silica nanoparticles（CFMSN）were synthesized by a sol-gel method and calcination.The nano-carriers were spherical particles with an average particle size of about 80nm and a pore volume of 0.52 cm³ g^-1,in which calcium and iron were uniformly distributed in the particles with contents of 2.37 and 1.29 wt%,respectively.CFMSN had calcium and iron ion release properties in response to the tumor microenvironment,which was essential for subsequent synergistic therapy.Dihydroartemisinin（DHA）was loaded into CFMSN by a nano-deposition method to prepare CFMSN@DHA with a loading content of about 16%.The performance of CFMSN@DHA in generating reactive oxygen species through multiple pathways was systematically investigated.In vitro and in vivo tests showed that CMFSN@DHA achieved efficient anti-tumor effects through the multimodal synergism of DHA-mediated chemotherapy,CFMSN/Fe²⁺and Fe²⁺-DHA-mediated chemodynamic therapy and Ca²⁺-DHA-mediated oncosis therapy.