Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance

Hai Wang (), Yutong Liang, Yue Yin, Jie Zhang, Wen Su, Alisa M. White, Jiang, Jiangsheng Xu, Yuntian Zhang, Samantha Stewart, Xiongbin Lu and Xiaoming He ()
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Hai Wang: University of Maryland
Yutong Liang: University of Maryland
Yue Yin: National Center for Nanoscience and Technology
Jie Zhang: National Center for Nanoscience and Technology
Wen Su: National Center for Nanoscience and Technology
Alisa M. White: University of Maryland
Jiang: University of Maryland
Jiangsheng Xu: University of Maryland
Yuntian Zhang: University of Maryland
Samantha Stewart: University of Maryland
Xiongbin Lu: Indiana University School of Medicine
Xiaoming He: University of Maryland

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-020-20588-0

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