Mapping Optimal Charge Density and Length of ROMP-based PTDMs for siRNA Internalization.

Mapping Optimal Charge Density and Length of ROMP-based PTDMs for siRNA Internalization.
Biomacromolecules. 2016 Sep 6;
Authors: Caffrey LM, deRonde BM, Minter LM, Tew GN
Abstract
A fundamental understanding of how polymer structure impacts internalization and delivery abilities of biologically relevant cargoes, particularly siRNA, is of critical importance to the successful design of improved delivery reagents. Herein we report the use of ring-opening metathesis polymerization (ROMP) methods to synthesize two series of guanidinium-rich protein transduction domain mimics (PTDMs): one based on an imide scaffold that contains one guanidinium moiety per repeat unit and another based on a diester scaffold that contains two guanidinium moieties per repeat unit. By varying both the degree of polymerization and, in effect, the relative number of cationic charges in each PTDM, the performances of the two ROMP backbones for siRNA internalization were evaluated and compared. Internalization of fluorescently labeled siRNA into Jurkat T cells demonstrated that FITC-siRNA internalization had a charge content dependence, with PTDMs containing approximately 40 to 60 cationic charges facilitating the most internalization. Despite this charge content dependence, the imide scaffold yielded much lower viabilities in Jurkat T cells than the corresponding diester PTDMs with similar numbers of cationic charges, suggesting that the diester scaffold is pref...

Source: Biomacromolecules - September 5, 2016 Category: Biochemistry Authors: Caffrey LM, deRonde BM, Minter LM, Tew GN Tags: Biomacromolecules Source Type: research