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

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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N2 - 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.

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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