Preparation And Characterization Of Responsive Amphiphilic Polycarbonate Nanomicelles

People have tried various methods to cure cancer,in recent years,responsive micelles have been used as drug carriers to control drug release and this method has obtained widespread attention from researchers at home and abroad.It can improve various drawbacks of traditional treatment methods,such as:reducing the toxicity of small molecule drugs to normal cells,improving the targeting of drugs,prolonging the efficacy of drugs and improving the solubility of drugs.Researchers have given different properties to micelles through different means,so that micelles can be better used as drug carriers.Due to the cellular environment difference between the cancer cells and normal cells,introduction of responsive functional groups can make micelles responsive in cancer cells.In order to reduce the toxicity of micelles to the human body,researchers generally choose aliphatic polyesters and the like to synthesize biodegradable drug carriers.In this paper,two different responsive polymers were synthesized and prepared into micelles to study their response properties and drug loading properties.（1）Using 3-methyl-3-hydroxymethyloxetane as a starting material,ring-opening reaction in the presence of hydrobromic acid（HBr） to form2,2-hydroxymethyl-3-bromopropane,and then the product teacts with ethyl chloroformate to form a bromine-containing six-membered cyclic carbonate（BC）,and the BC monomer is subjected to ring-opening polymerization to form a side group bromine-containing amphiphilic polymer mPEG₁₁₃-b-poly（BC）.Then,the selenium powder and sodium borohydride are reacted in an aqueous solution to form a sodium diselenide solution which reacts with the bromine atom in the amphiphilic polymer micelle to crosslink the micelle and impart oxidative responsiveness to the micelle.The confocal Raman microscope was used to characterize the diselenide bonds in the micelles to determine whether the micelles were crosslinked and to explore the oxidation responsiveness of the crosslinked micelles.The size and stability of the micelles were observed by dynamic light scattering（DLS）,and the morphology of the micelles was determined by transmission electron microscopy（TEM）.The critical micelle concentration（CMC）of the micelles was determined by fluorescence spectrometry.And the drug controlled release properties of the simulated drug Nile Red（NR）micelles were tested.（2）First,an alkynyl-containing diol is synthesized from 2,2-dimethylolpropionate and bromopropyne,and the product is reacted with ethyl chloroformate to form an alkynyl-containing six-membered cyclic carbonate（MPC）.The monomer of MPC is subjected to ring-opening polymerization to synthesize an alkyne-containing amphiphilic polymer mPEG₁₁₃-b-poly（MPC）.Secondly,2-nitrobenzyl alcohol and 6-bromohexanoic acid are esterified to form bromine-containing nitrobenzyl ester,which is reacted with sodium azide to convert bromine into azide.Finally,the nitrobenzyl ester was grafted to the polymer side by an Azide alkyne click reaction to form a photoresponsive polymer mPEG₁₁₃-b-poly（MPC）-g-NB.The change of micelles under ultraviolet light was detected by UV-visible spectrophotometer.The particle size and stability of micelles were measured by dynamic light scattering（DLS）.The critical micelle concentration（CMC）of micelles was determined by fluorescence spectrometer.