Photocatalytic Nano-Drug Loading System Based On Cobalt Phytate For Deep Drug Delivery And Anti-Tumor Therapy

In recent years,the high incidence and high fatality rate of malignant tumors pose a great threat to people’s life and health.With the rapid development of nanotechnology,nano-drugs have been used more and more in the treatment of cancer,but the curative effect is not good because of their low delivery efficiency in the tumor.Compared with normal tissue,there is a lack of mature lymphoid system in tumor tissue,and the retention of interstitial fluid leads to the increase of hydraulic pressure in tumor stroma.At the same time,cancer fibroblasts in tumor tissue secrete a large amount of collagen and promote the deposition of collagen in the tumor stroma,resulting in a significant increase in solid pressure between tumor cells,forming a dense matrix barrier,which makes it difficult to permeate and deliver drugs to the tumor.Therefore,reducing tumor interstitial pressure and relieving hypoxia are the key points to improve the anti-tumor effect of nano-drugs.Photocatalytic therapy is a kind of catalytic reaction in tumor excited by light,which can control the controllable activation and precise release of nano-drugs by adjusting the irradiation conditions of external laser.Reactive oxygen species（ROS）,a toxic metabolic product,are produced through the reaction,and apoptosis is induced.This treatment avoids the damage to human normal tissue in the process of treatment and improves the safety of treatment.Therefore,in this study,a nano-drug loading system（PRC@M）with photocatalytic activity was constructed to carry out effective anti-tumor therapy through coordination and cooperation with chemical kinetic therapy and photothermal therapy.In this study,a nano-drug loading system（PRC@M）with photocatalytic activity was constructed with cobalt phytate（Co PA）and resveratrol（Res）as the core.Among them,Co PA is a safe new photocatalyst,which can catalyze the decomposition of H₂O to O₂ under the near-infrared irradiation of 660nm,which can effectively reduce the interstitial hydraulic pressure（TIFP）of the tumor site,reduce the transvascular osmotic pressure difference and promote the drug to permeate into the tumor tissue.Res is a traditional chemotherapeutic drug,but it also has the function of inhibiting collagen secretion and deposition,thus reducing the solid pressure（TISP）at the tumor site.Here,the penetration and accumulation of drugs in the tumor site can be further promoted by simultaneously reducing TIFP and TISP.Firstly,the core-shell structure（PR）formed by Res encapsulated by polydopamine（PDA）with good biocompatibility was used as the carrier,then Co PA was loaded on the surface of PR,and finally the homologous cell membrane was wrapped on the surface of PRC to form a photocatalytic nano-drug loading system（PRC@M）with homologous targeting.The adhesion molecules specifically expressed on the membranes of homologous tumor cells are bound in the form of receptor-ligand,allowing nanodrugs to reach tumor tissues efficiently and achieving precise drug delivery while promoting drug uptake by cells.Under the near-infrared irradiation of 660 nm,PRC@M produces photothermal effect to promote the release of PRC and Res,and the nanomaterial PRC produces electron transition,resulting in electron-hole pairs,the hole reacts with H₂O to produce O₂.This process not only reduces the TIFP of the tumor site,but also alleviates the hypoxia of the tumor site,and promotes the penetration and accumulation of drugs in the tumor site.O₂ further captures electrons to form singlet oxygen ¹O₂,which induces tumor cell apoptosis.In addition,Co²⁺can also undergo a Fenton-like reaction with endogenous high-concentration H₂O₂ to generate hydroxyl radicals（·OH）,which can further kill tumor cells.Finally,the cooperative treatment strategy of photocatalytic therapy,chemical kinetic therapy and photothermal therapy have been better realized.