4.8 Article

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

期刊

JOURNAL OF CONTROLLED RELEASE
卷 332, 期 -, 页码 608-619

出版社

ELSEVIER
DOI: 10.1016/j.jconrel.2021.03.004

关键词

RNA interference; Cytocompatibility; siRNA delivery; Cationic nanoparticles; Responsive hydrogels; Nanogels

资金

  1. National Institutes of Health, United States [R01-EB022025, R01-EB000246]
  2. National Science Foundation, United States [1033746]
  3. Institute for Biomaterials, Drug Delivery, and Regenerative Medicine
  4. Cockrell Family Regents Chair Foundation
  5. Office of the Dean of the Cockrell School of Engineering at the University of Texas at Austin (UT)
  6. 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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