Cytocompatibility, membrane disruption, and siRNA delivery using environmentally responsive cationic nanogels

David S Spencer; Aaliyah B Shodeinde; David W Beckman; Bryan C Luu; Hannah R Hodges; Nicholas A Peppas

doi:10.1016/j.jconrel.2021.03.004

Cytocompatibility, membrane disruption, and siRNA delivery using environmentally responsive cationic nanogels

J Control Release. 2021 Apr 10:332:608-619. doi: 10.1016/j.jconrel.2021.03.004. Epub 2021 Mar 3.

Authors

David S Spencer¹, Aaliyah B Shodeinde¹, David W Beckman², Bryan C Luu², Hannah R Hodges², Nicholas A Peppas³

Affiliations

¹ McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX 78712, USA.
² McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA.
³ McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA; Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX 78712, USA; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, 2409 University Ave. Stop A1900, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX 78712, USA; Departments of Pediatrics, Surgery, and Perioperative Care, Dell Medical School, 1601 Trinity St., Bldg. B, Stop Z0800, Austin, TX 78712, USA. Electronic address: peppas@che.utexas.edu.

Abstract

Advances in the formulation of nucleic acid-based therapeutics have rendered them a promising avenue for treating diverse ailments. Nonetheless, clinical translation of these therapies is hindered by a lack of strategies to ensure the delivery of these nucleic acids in a safe, efficacious manner with the required spatial and temporal control. To this aim, environmentally responsive hydrogels are of interest due to their ability to provide the desired characteristics of a protective carrier for siRNA delivery. Previous work in our laboratory has demonstrated the ability to synthesize nanoparticle formulations with targeted pK_a, swelling, and surface PEG density. Here, a library of nanoparticle formulations was assessed on their in vitro toxicity, hemolytic capacity, siRNA loading, and gene-silencing efficacy. Successful candidates exhibited the lowest degrees of cytotoxicity, pH-dependent membrane disruption potential, the highest siRNA loading, and the highest transfection efficacies.

Keywords: Cationic nanoparticles; Cytocompatibility; Nanogels; RNA interference; Responsive hydrogels; siRNA delivery.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Cations
Nanogels
Nanoparticles*
RNA, Small Interfering
Transfection

Substances

Cations
Nanogels
RNA, Small Interfering

Abstract

Publication types

MeSH terms

Substances

Grants and funding