| Cancer is the common cause of death in the world.For chemotherapy,photothermal therapy and immunotherapy,the treatment concentration in tumor tissue is a key factor to determine the treatment efficiency.In view of this,the development of targeted drug delivery systems is important to selectively deliver drugs to tumor regions.Various types of nanomaterials have been widely used as drug carriers.However,the low tumor targeting ability of nanomaterials limits their clinical application.Due to the increased pressure of tumor interstitial fluid,nanomaterials are difficult to penetrate tumor tissue by passive diffusion.As biological vectors,bacteria can colonize and proliferate in tumors and inhibit tumor growth,making them ideal candidates for delivery vectors.Exosomes,as a natural carrier of intercellular communication,are characterized by high biocompatibility,immune evasion and innate interaction with tumor cells.Therefore,it is also ideal as a drug delivery carrier.Bioorthogonal labeling based on glucose metabolism engineering is becoming more and more important to modify the biological drug delivery system in vivo because of its advantages of high efficiency,specificity,nondestructive and stability.In this strategy,specific chemical reporter groups are introduced into the target through the glucose metabolism pathway,and then covalently connected with the compound carrying the paired group through the biological orthogonal reaction,o as to realize the coupling of the living biodelivery carrier with the target compound（dyes,cytokines,anticancer drugs）.Based on bacteria and Exosomes,different biological orthogonal glucose metabolism nano-drug delivery systems for tumor targeted therapy were constructed in this paper,and the effects of bacterial and Exosome drug delivery systems in tumor treatment were evaluated.（1）Construction and evaluation of hyaluronic acid nanoparticles delivery system coupled with attenuated Salmonella YB1 based on glucose metabolism modification.Chlorin E6（Ce6）loaded nanoparticles were constructed as tumor laser-mediated photodynamic therapy（PDT）and ultrasound-mediated sonodynamic therapy（SDT）nanoparticles,which were coupled to the surface of hypoxia-targeted attenuated live bacteria（YB1）by click chemical reaction.The results show that YB1’s targeting ability can deliver photoacoustic sensitizer to the hypoxic region deep in the tumor and enhance the effective storage of nanomedicine.The synergistic effect of 660 nm near-infrared laser excitation and ultrasound can realize the high accumulation of nano-drugs in the tumor hypoxia area and effectively reduce the therapeutic dose of nano-drugs and achieve tumor ablation.Meanwhile,the immunotherapy of bacteria can alleviate the tumor microenvironment and activate immune-related cells.（2）Construction of Exosome biomimetic nano drug delivery system.To construct a drug delivery system of NK Exosomes modified by glucose metabolism coupled with bacterium YB1.NK Exosomes have cytotoxicity and immune response,while YB1 bacteria have tumor hypoxia targeting ability.This system can target the tumor hypoxic region and realize the NK Exosomatic toxicity and the immunotherapy of YB1 bacteria... |
