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Sci Rep. 2017 Oct 27;7(1):14211. doi: 10.1038/s41598-017-14153-x.

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

Author information

1
Department of Biomedical Engineering-University of Wisconsin-Madison, Madison, WI, USA.
2
Department of Orthopedics and Rehabilitation-University of Wisconsin-Madison, Madison, WI, USA.
3
Department of Bioengineering & Therapeutic Sciences-University of California, San Francisco, San Francisco, CA, USA.
4
Roddenberry Center for Stem Cell Biology & Medicine-Gladstone Institutes, San Francisco, CA, USA.
5
Department of Biomedical Engineering-University of Wisconsin-Madison, Madison, WI, USA. wlmurphy@wisc.edu.
6
Department of Orthopedics and Rehabilitation-University of Wisconsin-Madison, Madison, WI, USA. wlmurphy@wisc.edu.
7
The Materials Science Program-University of Wisconsin-Madison, Madison, WI, USA. wlmurphy@wisc.edu.
8
The Stem Cell and Regenerative Medicine Center-University of Wisconsin-Madison, Madison, WI, USA. wlmurphy@wisc.edu.

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.

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