Responsive Metal-Organic Nanomaterials For Cancer Treatment

Metal-organic nanomaterials have been widely used in the field of biomedicine because of their clear tunable composition and structure,easy modification,good biocompatibility.However,it’s difficult to achieve accurate and efficient cancer treatment by using the metal organic nanomaterials,and will have adverse effects on normal tissues and organs.The design of responsive nanomaterials provides a new pathway to solve the above problems.Under the specific stimulation of the tumor microenvironment(TME),nanoparticles disassemble responsively and release the loaded drug molecules,which play therapeutic effect at the tumor site.However,the responsive nanoparticles remain stable and low activity under normal physiological conditions.After studying the characteristics of TME,herein,the research designed two kinds of responsive metal organic nanomaterials for drug delivery,from single acid response to co-response of weak acid,hydrogen peroxide(H2O2)and glutathione(GSH)of TME.The response sensitivity had been improved,and finally achieved selective treatment.The primary research contents are as follows:(1)A metal-organic layer ZIF-L was firstly synthesized.After adjusting the reaction conditions,NZIF-L with smaller and thinner size was prepared.DOX@NZIF-L and TCPE@NZIF-L were obtained by loading chemotherapy drug DOX and aggregation-induced emission(AIE)dye TCPE,respectively.The carrier NZIF-L was stable under neutral condition but dissociated responsively under weak acid condition,leading to the quick release of the drug molecules.DOX@NZIF-L and TCPE@NZIF-L could be rapidly internalized by cells,and achieved cell killing and bioimaging respectively.(2)Coordination polymer nanoparticles Fe-IBDP NPs were synthesized by one-step coordination self-assembly.Under normal physiological conditions,Fe IBDP NPs were stable and had no photoactivity.While under the stimulation of weak acid,H2O2 and GSH,the nanoparticles were rapidly disassembled in the cancer cells.Furthermore,Under the light irradiation,the dissociated IBDP photosensitizer produced a large amount of ROS to kill the cancer cells and achieved the activatable photodynamic therapy(PDT).The fabricated Fe IBDP NPs,which possessed activable photodynamic effect in response to TME,achieved selective cancer therapy,in which high phototoxicity against tumor cells and low toxicity against normal cells.