Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance
Authors: Jiangsheng Xu
Yuntian Zhang
Yue Yin
Jie Zhang
Alisa M White
Xiongbin Lu
Bin Jiang
Wen Su
Hai Wang
Samantha Stewart
Xiaoming He
Yutong Liang
Journal: Nature Communications (2021)
Discipline: Multidisciplinary
Keywords: P-glycoprotein; drug resistance; cancer; nanoparticle; tumor vasculature
Affiliations: Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA. ., CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China. ., University of Chinese Academy of Sciences, 100049, Beijing, China. ., Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA., CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China., Department of Medical and Molecular Genetics and Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA. ., Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, 20742, USA. .

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. 

Retracted: No

PubPeer comments:
 Two images in Figure 6b (left column) appear unexpectedly similar. ***  *** False color  , 
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