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

doi:10.1021/bc100149g

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

Pharmaceutical Materials and Soft Matter

Research output: Contribution to journal › Article › peer-review

46 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	156-168
Number of pages	13
Journal	Bioconjugate Chemistry
Volume	22
Issue number	2
DOIs	https://doi.org/10.1021/bc100149g
Publication status	Published - 16 Feb 2011

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10.1021/bc100149g

Cite this

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title = "Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery",

abstract = "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.",

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AU - Saeed, Aram O.

AU - Magnusson, Johannes P.

AU - Moradi, Emilia

AU - Soliman, Mahmoud

AU - Wang, Wenxin

AU - Stolnik, Snow

AU - Thurecht, Kristofer J.

AU - Howdle, Steven M.

AU - Alexander, Cameron

PY - 2011/2/16

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AB - 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.

U2 - 10.1021/bc100149g

DO - 10.1021/bc100149g

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