Study On Polypeptides To Promote The Penetration Of Nanomedicines In Tumor

Cancer is one of the most common causes of death in the world, and chemotherapy remains the primary treatment for cancer among conventional modalities. However, many chemotherapeutic agents have great limitations in clinical use, such as low selectivity and severe side effect. Conversely, nano-scaled drug delivery systems possess distinct advantages, including versatile functions, enhanced in vivo solubility, prolonged circulation time through avoiding rapid clearance by the renal and reticuloendothelial systems, low side effects, and improved tumor accumulation via the enhanced permeability and retention(EPR) effect. However, the therapeutic efficacy of nanomedicines to many solid tumors is limited by their poor penetration into tumor tissue. We have synthesized a series of polypeptides, attempt to study the effect of promoting the penetration of nanomedicines in tumor, to overcome the shortcomings in cancer chemotherapy.In this study, through N-Carboxyanhydride-(NCA)-ring-opening polymerization approach, P(CBZ-Lys)、P(CBZ-Orn) have been synthesized, after deprotection, PLys and POrn were obtained. After guanidination, P(Homo-Arg) and PArg were obtained. After that, these four polypeptides and PLG-g-mPEG formed micelles by electrostatic composite respectively. These four kinds of micelles were stable and uniform with no cytotoxicity, and these four polypeptides were found to have a significant effect on promoting blood vessel leakage.In this study, through N-Carboxyanhydride-(NCA)-ring-opening polymerization approach, random copolymers P[Glu(Bn)-co-Lys(Z)] and P[Glu(Bn)-co-Orn(Z)] with different feed ratios were prepared by adjusting the reactant ratio of BLG-NCA with ZLys-NCA and BLG-NCA with ZOrn-NCA, respectively. After P[Glu(Bn)-co-Lys(Z)] deprotection, P[Glu(Bn)-co-Orn(Z)] deprotection and guanidination, P(Glu-co-Lys) and P(Glu-co-Arg) were obtained, respectively. The zeta potential of the random copolymers could change with the pH of solution, suggestin the copolymers are pH-responsive. Through the determination of Pt content in Miles vascular leak test, it was found that this series of random copolymers obviously promote blood vascular leakage.