Construction And Performance Of Multifunctional Micro/Nano Transition Metal Carbonyl CO Releasing Molecules(CORMs) Composite System

As an important cell messenger molecule,carbon monoxide（CO）plays an important role in the treatment of many diseases,such as cancer,inflammation,kidney and liver injury.The use of carbon monoxide releasing molecules（CORMs）is a promising approach compared to direct inhalation of carbon monoxide gas for treatment.CORMs are chemically bound forms of CO pro-drugs that activate to release CO under certain conditions.However,it is an urgent problem to realize the controlled and targeted delivery of CORMs to the specific locations of biological targets and the on-demand release of CO.It is found that a more feasible method is to combine stable and fully functional nanocarriers to develop a multifunctional micro/nano CORMs composite system.Micro/nanomotors are a class of micro-machines that convert chemical energy（or other forms of energy）into their own mechanical energy.Thanks to their excellent autonomous driving capability,micro/nanomotors have promising applications in the fields such as environmental detection,biological sensing and drug therapy.Based on this,this paper designed and synthesized a multifunctional micro/nano transition metal carbonyl CO releasing molecules（CORMs）composite system with p H response,targeted recognition,fluorescence tracing and photo excitation to release CO according to the characteristics of weakly acidic tumor microenvironment.The main work finished is as follows:First,with UIO-66-NH₂as the skeleton and the multifunctional polymer coating FA-CHI-5-FAM as the blocking agent,the light-responsive transition metal carbonyl CORMs were loaded in the UIO-66-NH₂,resulting in the transition metal carbonyl CORMs composite system of UIO-66-NH₂/CORM@FA-CHI-5-FAM.The morphology and structure were characterized by XRD,SEM,BET,FT-IR,Zeta potential,thermal weight,fluorescence,etc.The CORMs composite system can release CO in response to p H stimulation target trigger in the tumor environment,with good anti-tumor activity.It provides a new reference for the design of a multifunctional micro/nano transition metal carbonyl CORMs composite system that integrates targeting and fluorescent tracing and can release CO through light control and p H stimulation response.Secondly,the FA-CHI targeted polymer blocking coating and catalytic metal platinum（Pt）were modified on the surface of hollow rare earth-based Tb-MOF,and the light-responsive transition metal-based CORMs were loaded.The bubble-driven Pt-Tb-MOF/CORM@FA-CHI nanomotor transition metal carbonyl CORMs composite system was prepared by layer-by-layer self-assembly technology.The asymmetric structure of the motors and the motion of the Janus motors were confirmed by SEM and fluorescence microscope.CO release studies indicate that this CORMs composite system has a short half-life of CO release in tumor micro-acids environments and a long half-life in normal physiological p H environments.CKK-8experiments showed that it has a lethal effect on tumor cells.This combination of p H response,visualization,and illumination control of release CO with autonomous motion provides new ideas for the design of multifunctional micro/nano transition metal carbonyl CORMs composite systems.Finally,the hollow SiO₂（HSiO₂）with a cavity and a cross-hole"window"was used as the carrier of the light responsive transition metal carbonyl CORMs and the coating of the FA-CHI-5-FAM has a targeted and fluorescent function,Pt on the surface by ion sputtering.Ultimately Janus Pt-HSiO₂/CORM@FA-CHI-5-FAM nanomotor transition metal carbonyl CORMs composite system was prepared.This CORMs composite system shown the faster CO release at lower p H and slow release at normal physiological p H,which can enable p H stimulation-response targeting to trigger carbon monoxide release.In addition,this system has the ability to kill cancer cells.The micro/nano transition metal carbonyl CORMs composite system integrating targeted control,fluorescence tracing,motor advantage,p H response and CO releasing is expected to be used for safe and efficient delivery of CORMs and further biological applications.