The Preparation Of Amphiphilic Block Polymer With Stimuli-responsive Elements And Research On The Its Properties

In the past Decades,nano-drug delivery systems,particularly stimuli-sensitive biodegradable polymeric nano-carriers,have been extensively explored for drug delivery of anticancer drugs.Amphiphilic po lymer is capable of self-assembly to nanostructure in aqueous,such as micelles and v esicles,which can be applied to load the medicine.Contrast to small molecule drug,this nanoscale polymeric micelles and vesicles possess several unique advantages,such as prolonged circulation time,increased the water solubility of the drug,improved drug availability,decreased adverse effects.However,the the therapeutic effects of traditional drug nano-carriers are usually restricted by slow and inefficient drug release at pathological site,the smart bio-responsive polymeric nano-carriers received great attentions.According to the different environment of tumor site and normal tissue environment,the polymer carrier that is responsive to external physical,chemical,biological and other stimuli can release anticancer drugs at a precise location.The integration of two different stimuli elements could fine-tune the drug release and augment therapeutic efficacy,which could be advantageous over mono stimuli responsive nano-particles.In this paper,we designed and synthesized two different biodegradable stimuli-sensitive polymer micelles and investigated the responsive performance.?1?First,two novel six-membered cyclic carbonate monomer,O-nitrobenzyl carbonated?MNC?and propargyl carbonated?MPC?,was synthesized from2,2-bis?hydroxymethyl?propionicacid,2-nitrobenzyl bromide,propargyl bromide andchloroformate.Second,amphiphilicblockcopolymer mPEG₁₁₃-b-poly?MNC_m-co-MPC_n?was synthesized by means of ring opening polymerization of MNC and MPC,using hydrophilic mPEG₁₁₃ as macroinitiator and DBU as catalyst.Third,core cross-linked polymer was synthesized via Azide-Alkyne clik chemistry between the pendant propargyl group in the hydrophobic and the cross-linker bis-?azidoethyl?disulfide.The molecular structure and molecular weight of mPEG₁₁₃-b-Poly?MNC_m-co-MPC_n?were measured and confirmed by ¹H NMR and gel permeation chromatography?GPC?.The morphology,CMC and responsive propeties were demonstrated by DLS,TEM,fluorescence spectroscopy and UV/vis spectroscopy.?2?First,a novel macromolecular RAFT reagent based on mPEG was synthesized through esterification reaction.The RAFT reagent was proved to be synthesized successfully through ¹H NMR and gel permeation chromatography?GPC?.Second,twonovelacrylatemonomer,2,2-dimethyl--5-methyl-5-methyl-5-acryloxymethyl-1,3-dioxacyclohexane?DMMA?and2-phenyl-5-methyl-5-acryloxymethyl-1,3-dioxacyclohexane?HMDPA?was synthesized.Third,amphiphilic block copolymer mPEG₁₁₃-b-poly?DMMA?/mPEG₁₁₃-b-poly?HMDPA?were synthesized by means of RAFT polymerization of DMMA/HMDPA,using hydrophilic macromolecular RAFT reagent and AIBN as initiation.The molecular structure and molecular weight of mPEG₁₁₃-b-poly?DMMA?/mPEG₁₁₃-b-poly?HMDPA?were measured and confirmed by ¹H NMR and gel permeation chromatography?GPC?.The diameter,CMC and responsive propeties were demonstrated by DLS,fluorescence spectroscopy.