Enzymatic-responsive Mesoporous Silica Nanoparticles For Dual-modality Imaging And Combination Of Chemotherapy And Photothermal Tumor Ablation

Currently,most chemotherapeutics,photosensitizers,and immune adjuvants are lacking in targeting,which leads to poor therapeutic efficacy and low safety.Therefore,the safe and efficient nano drug delivery system has always been a concern in the field of cancer treatment.In the present study,we developed hyaluronic acid?HA?-decorated magnetic mesoporous silica nanoparticles?M-MSN-HA?for sim?ltaneous tumor targeted delivery of near-infrared?NIR?dye indocyanine green?ICG?and Doxorubicin?DOX?to CD44-overexpressing cancer cells.The mutifunctinalized nanoparticles were denoted as M-MSN-HA/DI.The hyaluronic acid which possesses many features,including targeting and a capping agents which has enzyme-responsive is modified on the magnetic mesoporous silica surface by an amide reaction to load both chemotherapeutic drug DOX and photosensitizer ICG.HA can target tumor cells that highly express the CD44 receptor,and abundant hyaluronidase in tumor cells can specifically cleave HA,so as to achieve enzyme-responsive release of DOX and ICG.Also,the loaded Fe₃O₄ and ICG can be used as MRI contrast agents and photoacoustic imaging contrast agents to realize real-time monitoring of tumors.A variety of characterization experiments show that this synthesized nanoparticle M-MSN-HA/DI has good dispersibility and the particle size is about 355.3 nm.M-MSN-HA c has a good DOX and ICG load capabilities,and the photothermal heating capability of ICG after load is not suppressed.Confocal experiments showed that M-MSN-HA/DI has a more endocytosis in MDA-MB-231 cell which highly express the CD44 receptor comparing with free ICG and NIH-3T3 cell which is CD44recepter-negative.In vitro cytology experiments show that the particle has good biological safety and tumor synergistic treatment effect.In vitro experiments showed that the particles had good multi-modal imaging capabilities.In vivo experiments showed that the particles had good cancer treatment and multi-modal imaging capabilities capabilities.In summary,the M-MSN-HA/DI can realizes the integration of diagnosis and treatment of tumors.