2. Academic Validation
  3. Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance

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

  • Nat Commun. 2021 Jan 12;12(1):312. doi: 10.1038/s41467-020-20588-0.
Hai Wang 1 2 3,  Yutong Liang 4,  Yue Yin 5,  Jie Zhang 5,  Wen Su 5,  Alisa M White 4,  Bin Jiang 4,  Jiangsheng Xu 4,  Yuntian Zhang 4,  Samantha Stewart 4,  Xiongbin Lu 6,  Xiaoming He 7 8 9
Affiliations

Affiliations

  • 1 Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA. [email protected].
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China. [email protected].
  • 3 University of Chinese Academy of Sciences, 100049, Beijing, China. [email protected].
  • 4 Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
  • 5 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 100190, Beijing, China.
  • 6 Department of Medical and Molecular Genetics and Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • 7 Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA. [email protected].
  • 8 Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD, 21201, USA. [email protected].
  • 9 Robert E. Fischell Institute for Biomedical Devices, University of Maryland, College Park, MD, 20742, USA. [email protected].
PMID: 33436622 DOI: 10.1038/s41467-020-20588-0
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.

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