Self-delivery of a peptide-based prodrug for tumor-targeting therapy
self-assembly, self-delivery, prodrug, tumor-targeting therapy
A novel self-delivered prodrug system was fabricated for tumor-targeting therapy. In this nanosystem, the Arg-Gly-Asp-Ser (RGDS) tetrapeptide was used to improve the therapeutic index to integrin-overexpressing tumor cells. The antitumorous drug camptothecin was further appended to the ε-amino group of lysine by 20-O-succinyl linkage and controllably released via hydrolytic cleavage. Prodrug molecules self-assembled into fibrillar nano-architectures and achieved the capability of self-delivery after being injected subcutaneously into mice. Introduction of hydrophobic myristic acid favored the self-assembly and enhanced the cellular internalization of the prodrugs. In vitro and in vivo studies demonstrated that the self-assembled nanofibers could effectively target integrinoverexpressing tumorous cells and inhibit tumor growth via RGD-mediated specific targeting. Therefore, the traditional idea that fibrillar structures hold low therapeutic efficacy due to poor cell uptake can be challenged.
Tsinghua University Press
Mengyun Peng,Siyong Qin,Huizhen Jia,Diwei Zheng,Lei Rong,Xianzheng Zhang, Self-delivery of a peptide-based prodrug for tumor-targeting therapy. NanoRes.2016, 9(3): 663–673