Synthesis And Application Of Poly (Amino Acid)s With Functional Side-chains

In this paper we synthesized PEGylated poly(amino acid)s with functional side-chains via ring-opening polymerization(ROP)and obtained four types of poly(amino acid):mPEG-b-Poly(dithiane-glutamate),mPEG-b-Poly(Alklysine),mPEG-b-Poly(Vinyllysine)and mPEG-b-Poly(4-Bromobenzylalcohol-lysine)respectively.Propargyl alcohol can be easily connected to Poly(L-lysine)in this system by using carbonyl diimidazole(CDI)as a coupling reagent.The poly(L-lysine)which has reduction-sensitive side chains was prepared via Cu(I)-catalyzed azide-alkyne click reaction.Dynamic light scattering(DLS)was employed to measure the diameter of micelles fabricated from PEGylated poly(amino acid)s.The micelles,with an approximate diameter of 120 nm,are suitable for accumulation in tumor cells because of EPR effect.Transmission electron microscopy(TEM)test confirmed micelles' construction.In order to evaluate the anticancer effect,doxorubicin(DOX)was loaded into the micelles.The in vitro release experiment proved that the DOX-loaded micelles were stable under physiological environment.However,the presence of glutathione(GSH)leaded to a quick release of DOX.In vitro methyl thiazolyl tetrazolium(MTT)assays indicated that the polypeptides were biocompatible.Confocal laser scanning microscopy(CLSM)and flow cytometry measurements was used to exam the existence of GSH which enabled the enhanced DOX release in MCF-7 tumor cells.These tests proved that under a high concentration of GSH condition the loaded DOX would escape from the micelle more easily,and be released into the nucleus of tumor cells and cause cell death.Poly(amino acid)with functional side-chains will be a promising tool in cancer treatment.