Poly(ethylene glycol)-Conjugated PAMAM Dendrimer for Biocompatible, High-Efficiency DNA Delivery

Abstract

We demonstrate a simple and successful synthetic approach to devise a highly efficient DNA delivery system with low cytotoxicity and low cost. Polyamidoamine (PAMAM) dendrimer is a highly efficient DNA delivery agent, when compared to other chemical transfection reagents. Partially degraded, high-generation dendrimers offer even higher efficiency, presumably due to enhanced flexibility of the otherwise rigid dendrimer chains. We hypothesized that chemical modification of low generation dendrimer with biocompatible poly(ethylene glycol) (PEG) chains would create a conjugate of PAMAM core with flexible PEG chains, which mimics the fractured high-generation dendrimer and produces high transfection efficiency. Generation 5 PAMAM was modified with 3400 molecular weight PEG. The novel conjugate produced a 20-fold increase in transfection efficiency compared with partially degraded dendrimer controls. The cytotoxicity of PEGylated dendrimers was very low. This extremely efficient, highly biocompatible, low-cost DNA delivery system can be readily used in basic research laboratories and may find future clinical applications.

Brain-Targeting Mechanisms of Lactoferrin-Modified DNA-Loaded Nanoparticles

“…Lactoferrin is reported to be weakly cationic (Chasteen and Woodworth, 1990) and target Lf receptors in both the BBB and the neural cells (Huang et al, 2007a;Ji et al, 2006). In addition, PAMAM is cationic itself with primary amino groups on the surface (Kang et al, 2005;Luo et al, 2002;Patil et al, 2008). Thus, the synthesized Lf-modified vectors were also cationic.…”

siRNA transfection by dendritic core–shell nanocarriers

“…[169,174] PAMAM dendrimers consist of a multifunctional alkyl-diamine residue, tertiary amine branches that exert endosome buffering effects, and primary amino groups which participate in DNA binding due to their pKa values. [175][176] After Staudinger initiated the synthetic macromolecular revolution approximately eighty years ago with the introduction of the "macromolecular hypothesis", there were only three major polymer architectures/classes, namely, linear, cross-linked, and branched types.…”

Prospects for Gold Nanorod Particles in Diagnostic and Therapeutic Applications

“…PEG is a biocompatible polymer frequently used in drug and DNA delivery (Liu et al, 1999;Luo et al, 2002), and surface modification of gold nanorods with it also provides a degree of biocompatibility. Naturally, antibodies can be added on top of the PEG layer too (Liao and Hafner, 2005).…”