A supramolecular platform for controlling and optimizing molecular architectures of siRNA targeted delivery vehicles
Yuting Wen, Hongzhen Bai, Jingling Zhu, Xia Song, Guping Tang, Jun Li
Abstract
It requires multistep synthesis and conjugation processes to incorporate multifunctionalities into a polyplex gene vehicle to overcome numerous hurdles during gene delivery. Here, we describe a supramolecular platform to precisely control, screen, and optimize molecular architectures of siRNA targeted delivery vehicles, which is based on rationally designed host-guest complexation between a β-cyclodextrin-based cationic host polymer and a library of guest polymers with various PEG shape and size, and various density of ligands. The host polymer is responsible to load/unload siRNA, while the guest polymer is responsible to shield the vehicles from nonspecific cellular uptake, to prolong their circulation time, and to target tumor cells. A series of precisely controlled molecular architectures through a simple assembly process allow for a rapid optimization of siRNA delivery vehicles in vitro and in vivo for therapeutic siRNA-Bcl2 delivery and tumor therapy, indicating the platform is a powerful screening tool for targeted gene delivery vehicles.