Journal
JOURNAL OF CONTROLLED RELEASE
Volume 332, Issue -, Pages 608-619Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2021.03.004
Keywords
RNA interference; Cytocompatibility; siRNA delivery; Cationic nanoparticles; Responsive hydrogels; Nanogels
Funding
- National Institutes of Health, United States [R01-EB022025, R01-EB000246]
- National Science Foundation, United States [1033746]
- Institute for Biomaterials, Drug Delivery, and Regenerative Medicine
- Cockrell Family Regents Chair Foundation
- Office of the Dean of the Cockrell School of Engineering at the University of Texas at Austin (UT)
- National Science Foundation Graduate Research Fellowship Program [DGE-1610403]
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By evaluating a series of nanoparticle formulations, this study identified candidates with low cytotoxicity, pH-dependent membrane disruption potential, highest siRNA loading, and transfection efficacy for in vitro applications.
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 pKa, 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, pHdependent membrane disruption potential, the highest siRNA loading, and the highest transfection efficacies.
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