Self-assembly Of Peroxynitrite And Hydrogen Polysulfide Biosignal-responsive Polymers

Bioresponsive polymers are a class of smart materials that are sensitive to biological signals and have good potential for development in the field of precision medicine in the future.Therefore,such smart materials have always attracted people's attention.Currently,polymer systems that can respond to changes in physiological parameters such as p H,redox,hypoxia,enzymes,and mechanical responses have been widely used in drug de-livery,tissue engineering,and clinical treatment.Despite these advances,in order to meet the needs of precise medicine,we need to develop a response system for a certain bio-logical or pathological signal in order to facilitate the target treatment of related diseases.However,since it is difficult to synthesize polymers capable of recognizing a single en-dogenous molecule with high sensitivity and selectivity,and it is difficult to exclude in-terference from other intracellular analogs with similar structures and functions,there are few related studies.Among the many biological signals,active nitrogen?RNS?and active sulfur?RSS?are important biologically active substances and play a vital role in regulating nerve sig-nal transduction.Combining with the research foundation of the predecessors,this work uses ONOO-and H2Sn as the stimulus sources to carry out the synthesis,performance research and related applications of the corresponding polymer assemblies.1.We reported the synthesis of an ONOO^--unstable phenyl methacrylate monomer containing trifluoromethyl ketone group?MATFK?.Because the monomer was composed of a strong electron-withdrawing trifluoromethyl ketone group and the adjacent phenyl ester spacer,ONOO^-tended to oxidize the ketone to ethylene oxide,and then performed intramolecular elimination to break the phenyl ester key.PEO-b-PMATFK could be ob-tained by incorporating this special monomer into the polymer PEO-Br.We speculated that after ONOO^-initiation,the copolymer might be cleaved at a specific position in MATFK.This cleavage would disrupt the balance of amphiphilic properties of the poly-mer,thereby achieving ONOO^-responsive cleavage of the assembly.In order to apply it to biological cell experiments,we further introduced rhodamine fluorescent group?TMR?into the block copolymer to obtain PEO-b-P?MATFK-co-TMR?.Through cell imaging experiments,we could quantitatively monitor the intracellular dynamic change of ONOO^-,and the ONOO^-detection limit of micelles could be as low as about 10 n M.2.We synthesized a new amphiphilic block copolymer composed of polyethylene oxide and p-fluoronitrobenzoate functional group PEO-b-PFNB.The FNB unit could undergo aromatic nucleophilic substitution through H₂S_n to form a persulfide intermedi-ate,which immediately attacked the adjacent benzoate ester to generate a five-membered cyclic benzodithione and cleaved the benzoyl bond.The strong electron-withdrawing ni-tro group enhanced the nucleophilic nature of the fluorine site.The cyclization step?un-stable four-membered ring?could not occur in other RSSs with only one thiol group.This maked the PEO-b-PFNB copolymer highly identifiable to H₂S_n biosignals.In addition,polymers in aqueous media could self-assemble into special rod-shaped nanoparticles.Its one-dimensional shape was beneficial to prolong the circulation cycle in the body and became a nanocarrier.These polymerized nanorods would exhibit the required micelle dissociation under biostimulation of H₂S_n,thereby achieving specific drug delivery in a pathological environment.