Rational Design Of Multifunctional Drug-Loaded Silica Nanosystems As Cancer Theranostic Agents

Cancer is an urgent problem remaining to be solved in the field of medicine.Up to now,with the rapid development of nanotechnology,new applications have emerged in the field of biomedicine.Nano-carrier,which can provide a new opportunity for the early diagnosis and effective treatment of tumors,is one of the most promising research directions of tumor therapy.In recent years,mesoporous silica nanoparticles?MSNs?as drug delivery systems have attracted much attention due to their low toxicity,uniform and adjustable pore size,large specific surface area,stable skeleton structure and modifiable surface.However,due to its poor degradation,biosafety of MSNs has been criticized by researchers.In this paper,we carried out functional MSNs nanomaterials as the delivery system of chemotherapeutic drugs and other guest molecules.The specific findings are as follows:1.Herein,we used three different types of polymers with a cancer-targeting RGD to decorate MSNs and the functionalized nanosystems were used as drug carriers of oxaliplatin?OXA?.The results showed that polymer-surface decoration of the MSNs nanosystem by poly ethylene glycol?PEG?and polyethyleneimine significantly enhanced the anticancer efficacy of OXA,which was much higher than that of chitosan?CTS?.This effect was closely related to the enhancement of the cellular uptake and cellular drug retention.Moreover,PEI@MSNs-OXA possessed excellent advantages in penetrating ability and inhibitory effects on SW480 tumoral spheroids that were used to simulate the in vivo tumor environments.Therefore,this study provides useful information for the rational design of a cancer-targeted MSNs nanosystem with polymer-surface decoration.2.Then,we synthesized rod-like silica and constructed rod-like silica nano-drug loading system MSNRs-DOX.Compared with the traditional spherical silica nanoparticles,the nanorod drug loading system has a larger surface area and transmembrane transport rate,resulting in better permeability of nanorod system into the tumor to obtain higher drug loading and antitumor activity.MSNRs-DOX nanosystem inhibits the growth of CNE-2 cells and activates the caspase family by inducing apoptosis.Downstream p53,AKT and MAPKs signaling pathways were activated by inducing cells to accumulate a large number of ROS.The results of imaging and anti-tumor experiments in vivo showed that the targeting effect of MSNRs-DOX enhanced the accumulation and permeability of DOX in tumor area,effectively increasing the inhibitory effect of DOX on tumor proliferation.3.Then,based on the properties of tumor hypoxia,we designed and synthesized an oxygen-carrying nanosystem O₂-PIr@Si@PDA,using PLGA nanospheres coated with oxygen carrier PFOB and hypoxic probe iridium complex as the core and silica as a shell.At the same time,menthol was used as sealing agent to realize the sealing of oxygen.The polydopamine,which coated on the surface of the nanosystem,would heat up under the irradiation of laser?808 nm?,resulting in a large amount release of oxygen and the rupture of the silicon shell.The nanosystem can effectively solve the problem of tumor hypoxia to improve the effect of radiotherapy.This result showed that the multifunctional nano-system O₂-PIr@Si@PDA can be used as an efficient and low-toxic radiosensitizer to achieve radiotherapy and chemotherapy of tumors in vitro and in vivo.4.Dendritic MSNs with large pore size and low silicon-oxygen crosslinking degree was designed and synthesized by interfacial synthesis method,and the in-situ growth of bismuth selenide on silicon surface was realized by coordination method.Then the dendritic MSNs was used to load catalase and immune adjuvant CPG-OND,to realize the co-loading of enzyme and DNA,and constructed the nano-system of Bi₂Se₃@Si O₂@CAT-CPG.The nanosystem can decompose hydrogen peroxide in tumor to produce oxygen for enhancement of X-ray radiotherapy efficacy,and realize the combination of radiotherapy and immunotherapy.