Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery

Aram O. Saeed, Johannes P. Magnusson, Emilia Moradi, Mahmoud Soliman, Wenxin Wang, Snow Stolnik, Kristofer J. Thurecht, Steven M. Howdle, Cameron Alexander

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46 Citations (Scopus)


Multifunctional and modular block copolymers prepared from biocompatible monomers and linked by a bioreducible disulfide linkage have been prepared using a combination of ring-opening and atom-transfer radical polymerizations (ATRP). The presence of terminal functionality via ATRP allowed cell-targeting folic acid groups to be attached in a controllable manner, while the block copolymer architecture enabled well-defined nanoparticles to be prepared by a water−oil−water double emulsion procedure to encapsulate DNA with high efficiency. Gene delivery assays in a Calu-3 cell line indicated specific folate-receptor-mediated uptake of the nanoparticles, and triggered release of the DNA payload via cleavage of the disulfide link resulted in enhanced transgene expression compared to nonbioreducible analogues. These materials offer a promising and generic means to deliver a wide variety of therapeutic payloads to cells in a selective and tunable way.
Original languageEnglish
Pages (from-to)156-168
Number of pages13
JournalBioconjugate Chemistry
Issue number2
Publication statusPublished - 16 Feb 2011

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