Tumor-targeted gene delivery using molecularly engineered hybrid polymers functionalized with a tumor-homing peptide

Bioconjugate Chemistry
Kris C WoodPaula T Hammond

Abstract

Before gene therapy can be used in clinical settings, safe and efficient DNA delivery systems must be developed to overcome a range of extra- and intracellular transport barriers. As a step toward the development of a modular, multifunctional gene delivery system to overcome these diverse barriers, we have developed a family of linear-dendritic "hybrid" polymers which contain functionalities for tissue targeting, minimization of nonspecific interactions, endosomal buffering, and DNA binding. Here, we demonstrate the rapid three-step, room-temperature, aqueous synthesis of hybrid polymers, as well as the functionalization of these polymers with a peptide targeting ligand that specifically binds to glucose-regulated protein-78 kDa (GRP-78), a clinically relevant tumor antigen identified in human cancer patients. These polymer systems can condense plasmid DNA into small nanoparticle structures (<210 nm) and transfect cells expressing GRP-78 with efficiencies that exceed that of branched polyethylenimine (bPEI), one of the best commercially available polymers for in vitro transfections. The synthetic approach described here may be useful for the rapid synthesis and optimization of polymer gene delivery systems bearing a range of di...Continue Reading

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Citations

Jul 19, 2011·Bioconjugate Chemistry·Daniel K BonnerPaula T Hammond
Aug 16, 2011·ACS Nano·Vladimir V ShuvaevVladimir R Muzykantov
Jun 6, 2008·Gene Therapy·D Schaffert, E Wagner
Aug 7, 2009·Journal of Biomechanical Engineering·Todd O PangburnEfrosini Kokkoli
Sep 6, 2012·Therapeutic Delivery·Ryan M PearsonSeungpyo Hong
Feb 25, 2009·Expert Opinion on Drug Delivery·Constantinos M PaleosDimitris Tsiourvas
May 9, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rajeev K TyagiTejram Sahu
Oct 24, 2009·Biomaterials·Todd J HarrisSangeeta N Bhatia
Dec 23, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Wing-Fu Lai, Marie Chia-Mi Lin
Jun 3, 2008·Trends in Biotechnology·Nuria Sanvicens, M Pilar Marco
Oct 6, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Vladimir V ShuvaevVladimir R Muzykantov
Oct 1, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yu ZhangRichard A Gemeinhart
May 30, 2015·Colloids and Surfaces. B, Biointerfaces·Ali Dehshahri, Hossein Sadeghpour
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Jan 13, 2009·Macromolecules·Shuang LiuKristi L Kiick

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