Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance
Author
Wang, H.Liang, Y.
Yin, Y.
Zhang, J.
Su, W.
White, A.M.
Jiang, B.
Xu, J.
Zhang, Y.
Stewart, S.
Lu, X.
He, X.
Date
2021-01-12Journal
Nature CommunicationsPublisher
Nature ResearchType
Article
Metadata
Show full item recordAbstract
The transmembrane P-glycoprotein (P-gp) pumps that efflux drugs are a major mechanism of cancer drug resistance. They are also important in protecting normal tissue cells from poisonous xenobiotics and endogenous metabolites. Here, we report a fucoidan-decorated silica-carbon nano-onion (FSCNO) hybrid nanoparticle that targets tumor vasculature to specifically release P-gp inhibitor and anticancer drug into tumor cells. The tumor vasculature targeting capability of the nanoparticle is demonstrated using multiple models. Moreover, we reveal the superior light absorption property of nano-onion in the near infrared region (NIR), which enables triggered drug release from the nanoparticle at a low NIR power. The released inhibitor selectively binds to P-gp pumps and disables their function, which improves the bioavailability of anticancer drug inside the cells. Furthermore, free P-gp inhibitor significantly increases the systemic toxicity of a chemotherapy drug, which can be resolved by delivering them with FSCNO nanoparticles in combination with a short low-power NIR laser irradiation. Copyright 2021, The Author(s).Sponsors
This work was supported by grants from the National Institutes of Health (NIH R01CA206366 and R01CA243023).Keyword
drug efflux pumpsmulti-drug resistant cancer cells
P-glycoprotein inhibition
tumor vasculature targeted nanovesicle
Identifier to cite or link to this item
http://hdl.handle.net/10713/15179ae974a485f413a2113503eed53cd6c53
10.1038/s41467-020-20588-0