The Design And Synthesis Of Light-responsive Polymer Nanocarriers And Application For Cancer Therapy

Realizing the control of drug release,increasing drug expression of the lesion,reducing the leakage of drugs and the occurrence of adverse reactions,is currently new strategy of anti-tumor agents research.The advantage of non-invasive manipulating with high spatiotemporal resolution of light-control technology makes it favourable in bio-applications,and light-control technology shows a big advantage in control of drug release.Therefore,we employed the light-regulated drug release as the breakthrough,synthesised a series of light-responsive biodegradable polymeric micelles based on o-Nitrobenzyl phototrigger,used as a nanocarrier of doxorubicin（DOX）or paclitaxel（PTX）and light-regulated release,achieving efficient antitumor effect.The main contents are detailed as follows:1.The synthesis of Light-responsive chitosan oligosaccharide micelle and PEG micelle nanocarriers loaded in PTX and Application for Cancer Therapy.We synthesized two light-responsive amphiphilic block copolymer —— COS-NMDB and PEG-NMDB based on Chitosan Oligosaccharide and PEG.we evaluated the photocontrollable release and antitumor effects of PTX/COS-NMDB_7.5 in vitro.We studied the characteristics of PEG-NMDB micelles and loptical properties.First,we synthesized a phototrigger（NMDB-ester）,preparing a number of COS-NMDB with different graft numbers through amide reaction.The structure was characterized by Infrared spectroscope（FT-IR）and Nuclear magnetic resonance.Through characterising the Properties of size,PDI,CMC and stability,we selected the suitable one.PTX could be loaded inside the micelles,and the entrapment efficiency and loading efficient was 76.55±11.60% and 14.46±2.20%,respectively.Then,we proved the optical properties included photodissociation reaction and control release under irradiation condition.In vitro release experiments,the longer the illumination time,the more and the faster drug release.PTX/COS-NMDB_7.5+hv showed enhanced cytotoxicity than PTX and PTX/COS-NMDB_7.5-hv.A photo-responsive amphiphilic block copolymer — Polyethylene glycol-S-（o-nitro-m-methoxy-p-dodecone alkoxy benzyl ester）（PEG-NMDB）was synthesized based on NMDB-ester and polymer PEG1000-NH2.PEG-NMDB could self-assemble into polymer micelles in deionized water,and the size was determined by Malvin particle size analyzer and Transmission electron microscopy（TEM）.The change of absorption spectrum along with the illumination was studied via Ultraviolet-visible spectroscopy（UV-vis）.Model drug Nile red could be loaded inside the micelles to prove the control release under irradiation condition.All of this proved PEG-NMDB has potential application in biology.2.NIR-responsive PEG-NMAB-PLA copolymer upconversion composite nanoparticles loaded in DOX for Cancer Therapy in vitro and in vivo.We synthesized a 980 nm NIR-trggered nano-composites — PNP-UC for DOX photocontrollable release.And we evaluated the drug release and antitumor effects in vitro and in vivo.First,we synthesized a phototrigger（NMAB-ester）,usd as the connections of PEG and PLA,preparing a number of PEG-NMAB-PLA（PNP）with different hydrophobic/hydrophilic moieties.Through characterising the Properties of size,PDI,CMC,entrapment efficiency and loading efficient,we selected the suitable one for loading DOX and UCNPs.The entrapment efficiency and loading efficient was 62.85±9.90% and 6.07±0.849%,respectively.We proved the optical properties included photodissociation reaction and control release under irradiation condition.Finally,we proved that when there were NIR light,UC and phototrigger in same time,PNP-DOX-UC could show the fast release and strong cytotoxicity in vitro.In vivo studys,PNP-DOX-UC+hv showed high anti tumor effiency and low toxicity.