Wang, HaiLiang, YutongYin, YueZhang, JieSu, WenWhite, Alisa M.Jiang, BinXu, JiangshengZhang, YuntianStewart, SamanthaLu, XiaongbinHe, Xiaoming2022-05-102022-05-102021-01-12Wang H, Liang Y, Yin Y, et al. Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance. Nat Commun. 2021;12(1):312. Published 2021 Jan 12. doi:10.1038/s41467-020-20588-0https://hdl.handle.net/1805/28932The 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.en-USAttribution 4.0 InternationalCancer therapyNanomedicineNanoscale materialArticle