A Synergistic Anti-cancer Research Of Stimulation Responsive Drug Delivery System Based On Near-infrared Light

Polymeric nanoparticles have a widely applications in biomedical diagnosis and treatment owe to its various advantages such as facile preparation,easy surface modification,and physical property adjustment.Thus,in recent years,nanoparticles attracted biomedical researchers' interest,particularly as anti-cancer drug delivery nanocarriers.In this thesis,we prepared amphiphilic block polymer via living/controlled free radical polymerization and Diels-Alder reaction,then used them to load anticancer drugs.In order to improve anti-cancer efficacy,we simultaneously encapsulated photothermal effect molecules to strengthen the anti-cancer effect.Notably,near-infrared light(NIR)possessed great advantages for light-responsive controllable drug release,such as deep tissue penetration and low damage to healthy tissues.Herein,a NIR-responsive drug delivery system is developed based on a NIR dyes,indocyanine green(ICG),and an anti-cancer drug,doxorubicin(DOX),so that NIR and Diels-Alder reaction can synergistically work in this system.In the system,ICG can convert light to heat to kill cancer cells and simultaneously achieved retro Diels-Alder reaction,so that the micelles relaxed and release drug under NIR irradiation.Finally,significant synergistic effect of NIR-triggered drug release,photothermal and chemo-therapy can be achieved by single NIR exposure.This thesis contains three sections as follows:1.Design and Preparation of Amphiphilic Block Copolymers.Firstly,a compound containing furan and N-octyl maleimide were selected as original materials for using Diels-Alder reaction.Poly(oligo(ethylene glycol)methacrylate)(OEGMA)was used as hydrophilic segment of amphiphilic block copolymer.POEGMA was prepared by reversible addition-fragmentation chain-transfer(RAFT)polymerization.Compound containing furan group was used as hydrophobic segment which was prepared by using POEGMA as macro chain transfer agent to prepare amphiphilic polymers with different compositions.Finally,N-octylmaleimide was appended onto the side chain via Diels-Alder reaction..2.Characterization of Micelles,Drug Encapsulation and Release.Micelles were prepared through nano-precipitation and characterized the micelles using transmission electron microscope(TEM),dynamic light scattering(DLS)and critical micelle concentration(CMC).Based on the data,the suitable group were choosed to conduct the following drug encapsulation.Both drug loading content(DLC)and encapsulate loading content(ELC)were tested.The drug release from micelles in PBS was studied by a dialysis method in a humidity chamber upon a NIR irradiation.3.Anticancer Efficacy and Intracellular DistributionThe.anti-cancer effect in vitro were tested through(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)(MTT)assay and(confocal laser scanning microscopy)(CLSM)investigation.We tested drug-loaded micelles in the MTT experiment and the blank micelles as the control.The control group demonstrated that the blank micelles did not have cytotoxicity even in a high concentration(120 ?g/ml)while the experimental group showed at the drug concentration of 5.0 ?g/ml DOX and 10.0 ?g/ml ICG,respectively,the cell viability were decreased to 25%.CLSM images indicated that micelles loading both ICG and DOX can release DOX to nuclear effectively by photothermal effect-triggered drug release and ICG were mainly distributed in cytoplasm.