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Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy

Karlsson, Johan; Tzeng, Stephany Y.; Hemmati, Shayan; Luly, Kathryn M.; Choi, Olivia; Rui, Yuan; Wilson, David R.; Kozielski, Kristen L.; Quiñones-Hinojosa, Alfredo; Green, Jordan J.

Abstract:
Clinical translation of polymer‐based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA‐mediated knockdown in both glioma and melanoma cells in high‐serum conditions compared to non‐crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue‐mediated siRNA delivery beyond the liver, unlike conventional nanoparticle‐based delivery. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000130532
Veröffentlicht am 19.03.2021
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Funktionelle Grenzflächen (IFG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 1616-301X, 1057-9257, 1099-0712, 1616-3028
KITopen-ID: 1000130532
Erschienen in Advanced Functional Materials
Verlag Wiley-VCH Verlag
Schlagwörter bioreducible; crosslinking; nanoparticles; siRNA; stimuli‐responsive polymers
Nachgewiesen in Scopus
Web of Science
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