Title
One-dimensional Poly(L-Lysine)-block-Poly(L-Threonine) Assemblies Exhibit Potent Anticancer Activity by Enhancing Membranolysis
Author
Yu-Fon Chen, Ai-Li Shiau, Sue-Joan Chang, Nai-Shin Fan, Chung-Teng Wang, Chao-Liang Wu, Jeng-Shiung Jan
Year
2017
Journal
Acta Biomaterialia
Abstract
Herein, we report the oncolytic activity of cationic, one-dimensional (1D) fibril assemblies formed from coil-sheet poly(L-lysine)-block-poly(L-threonine) (PLL-b-PLT) block copolypeptides for cancer therapy. The 1D fibril assemblies can efficiently interact with negatively charged cellular and mitochondrial membranes via electrostatic interactions, leading to necrosis via membrane lysis and apoptosis via the mitochondria-lytic effect. The concept is analogous to that of 1D drug carriers that exhibit enhanced cell penetration. In comparison to free PLL chains, PLL-b-PLT fibril assemblies exhibit selective cytotoxicity toward cancer cells, low hemolysis activity, enhanced membranolytic activity, and a different apoptosis pathway, which may be due to differences in the peptide-membrane interactions. Antitumor studies using a metastatic LL2 lung carcinoma model indicate that the fibril assemblies significantly inhibited tumor growth, improved survival in tumor-bearing mice and suppressed lung metastasis without obvious body weight loss. An additive efficacy was also observed for treatment with both PLL-b-PLT and cisplatin. These results support the feasibility of using 1D fibril assemblies as potential apoptotic anticancer therapeutics.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Polymers, Materials, Biochemistry