Journal
NANO TODAY
Volume 50, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2023.101878
Keywords
Fullerene; siRNA; Inhalation; PD-L1; Metastatic lung cancer
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A fullerene-based nanocomplex was designed for the inhalation delivery of siRNA, which protects siRNA against degradation, improves cellular uptake and gene knockdown efficiency, and prolongs pulmonary retention. By packaging PD-L1 siRNA, this nanocomplex significantly inhibits the progression of metastatic lung cancer in a mouse model without obvious adverse events and toxicity. This fullerene-based nanocomplex opens up the possibility of siRNA for treating a diverse range of pulmonary diseases.
Non-hepatic delivery of small interfering RNA (siRNA) remains a challenge for the development of RNA interference (RNAi)-based therapeutics. Inhalation is a straightforward and highly efficient route of deli-vering drugs to airways and pulmonary parenchyma, thus offering an opportunity for the novel paradigm of siRNA to treat lung diseases. Herein, we designed a fullerene-based nanocomplex to achieve the pulmonary delivery of siRNA via inhalation. The obtained nanocomplex protects encapsulated siRNA against nucleases degradation, improves the cellular uptake and gene knockdown efficiency, and prolongs the pulmonary retention of siRNA after inhalation. Through the package of programmed death-ligand 1 (PD-L1) siRNA, this nanocomplex significantly inhibits the progression of metastatic lung cancer without obvious adverse events and toxicity in a mouse model. This fullerene-based nanocomplex could open up the possibility of siRNA for treating a diverse range of pulmonary diseases.(c) 2023 Elsevier Ltd. All rights reserved.
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