Functionalization of microparticles with mineral coatings enhances non-viral transfection of primary human cells

Scientific Reports
Andrew S KhalilWilliam L Murphy

Abstract

Gene delivery to primary human cells is a technology of critical interest to both life science research and therapeutic applications. However, poor efficiencies in gene transfer and undesirable safety profiles remain key limitations in advancing this technology. Here, we describe a materials-based approach whereby application of a bioresorbable mineral coating improves microparticle-based transfection of plasmid DNA lipoplexes in several primary human cell types. In the presence of these mineral-coated microparticles (MCMs), we observed up to 4-fold increases in transfection efficiency with simultaneous reductions in cytotoxicity. We identified mechanisms by which MCMs improve transfection, as well as coating compositions that improve transfection in three-dimensional cell constructs. The approach afforded efficient transfection in primary human fibroblasts as well as mesenchymal and embryonic stem cells for both two- and three-dimensional transfection strategies. This MCM-based transfection is an advancement in gene delivery technology, as it represents a non-viral approach that enables highly efficient, localized transfection and allows for transfection of three-dimensional cell constructs.

References

Mar 23, 1990·Science·J A WolffP L Felgner
Apr 21, 1999·Biochimica Et Biophysica Acta·A HaberlandM Böttger
Aug 10, 2000·Nature Biotechnology·D Luo, W M Saltzman
Aug 28, 2001·Journal of Biomedical Materials Research·Y LiuK de Groot
Jan 18, 2003·Journal of Pharmaceutical Sciences·Christopher M Wiethoff, C Russell Middaugh
Jul 20, 2004·Nature Materials·Hong ShenW Mark Saltzman
Jan 18, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Diana TrentinHeike Hall
May 3, 2005·Journal of Pharmacological and Toxicological Methods·Philip Thomas, Trevor G Smart
Feb 15, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Tiffany Houchin-RayLonnie D Shea
May 24, 2007·Tissue Engineering·Arimichi OkazakiYasuhiko Tabata
May 15, 2008·The Journal of Investigative Dermatology·Jeffrey M Davidson
Aug 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jennifer E PhillipsAndrés J García
Oct 17, 2009·The AAPS Journal·Mohammed S Al-Dosari, Xiang Gao
Feb 18, 2010·ACS Applied Materials & Interfaces·Leenaporn JongpaiboonkitWilliam L Murphy
Mar 23, 2010·Acta Biomaterialia·Siyoung Choi, William L Murphy
Jun 24, 2010·Expert Reviews in Molecular Medicine·Christopher H Evans
Jun 25, 2010·Journal of Biomedical Materials Research. Part a·Darilis Suárez-GonzálezWilliam L Murphy
Oct 14, 2010·Advanced Materials·Jae Sung LeeWilliam L Murphy
Feb 5, 2011·Current Drug Delivery·Mahmoud ElsabahyMarianna Foldvari
May 18, 2011·Cold Spring Harbor Perspectives in Biology·Helge Ewers, Ari Helenius
Sep 20, 2011·Biomaterials·Benjamin K K TeoEvelyn K F Yim
Oct 22, 2011·Biomaterials·Darilis Suárez-GonzálezWilliam L Murphy
Nov 1, 2011·Advanced Materials·Jae Sung LeeWilliam L Murphy
Dec 14, 2011·Acta Biomaterialia·Darilis Suárez-GonzálezWilliam L Murphy
Mar 17, 2012·Molecular Pharmaceutics·Meghan J ReillyMillicent O Sullivan
Aug 10, 2013·Integrative Biology : Quantitative Biosciences From Nano to Macro·Anandika DhaliwalTatiana Segura
Dec 20, 2013·Tissue Engineering. Part a·Darilis Suárez-GonzálezWilliam L Murphy
Oct 25, 2014·Advanced Functional Materials·Xiaohua YuWilliam L Murphy
Dec 30, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xiaohua Yu, W L Murphy
Apr 25, 2015·Cell·Diego S D'AstolfoNiels Geijsen

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Methods Mentioned

BETA
transfection
high
transfect
transfecting
transfections
biopsy

Software Mentioned

GraphPad Prism
Adobe Photoshop

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