Anti-tumor Performance And Synthesis Of Stimuli Responsive Polymer-peptide

The major challenge in current cancer chemotherapeutics is to maximize therapeutic effect and evaluate tumor progression.Nano-materials have great application value in the field of cancer treatment due to its unique properties.The environment-responsive polymer as a new type of functional material which could be responsive to extexernal stimuli could be used as anticancer drug carrier and has become the hot research in biomedical field.Anti-cancer drugs composed of environment-responsive polymer and peptides with diverse biological functions could achieve drug targeting,long half-life in the blood circulation and high anti-tumor performance.In addition to improve the anti-tumor activity,cancer treatment evaluation also has the very vital significance.To address these challenges,we synthesized the ROS and pH dual responsive amphiphilic poly??-thioester?s copolymers D-D-P,and the structures of the polymers were confirmed by ¹H NMR,and the number molecular weight of the copolymer D-D-P was measured by GPC?M_n?50400?.D-D-P could self-assemble into nanoparticles in aqueous environment due to the amphiphilicity and the morphology and size of D-D-P nanoparticles were observed by transmission electron microscopy?TEM?and dynamic light scattering?DLS?showing that the number size distribution of nanoparticles was around 280 nm.The disassembly behaviors of D-D-P nanoparticles were investigated by the change of the nanoparticle size,NR fluorescence spectra and the DOX encapsulated D-D-P nanoparticles UV absorption spectra under pH 5 and ROS environment conditions,and the release of DOX were further proved in MCF-7 cells.To improve the anti-tumor activity,we synthesized the hydrophobic copolymer conjugate cytotoxic peptide?KLAKLAK?₂?named KLAK?and hydrophilic polyethylene glycol?PEG?froming ROS-sensitive H-P-K,which could self-assembly into micelle-like nanoparticles by copolymer backbones as cores and PEG and KLAK as shells to improve the cellular internalization and accumulation.The cytotoxicity data demonstrated that this nanoparticle design strategy increases the anti-tumor activity by⁴00 times in comparison to free peptide KLAK.The higher anti-tumor activity of nanoparticles proved by experiments was due to the effective for disruption of mitochondrial membranes and subsequent excessive ROS production in cells inducing cell apoptosis.To realize the ROS monitoring and treatment evaluation,we encapsulated squaraine?SQ?dyes as built-in reporters in ROS-sensitive H-P-K micelles.The nanoparticles could be stimulated by reactive oxygen species?ROS?which overexpressed in mitochondria of most cancers to release SQ,which formed H-aggregates and obtained the increased the photoacoustic?PA?signal.Taken together,this uniquely engineered nanoparticle has great potential for high anti-tumor performance and in situ treatment evaluation.