P-Glycoprotein-Targeted Photothermal Therapy of Drug-Resistant Cancer Cells Using Antibody-Conjugated Carbon Nanotubes
- Xubin SuoXubin SuoDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, ChinaMore by Xubin Suo,
- Brittany N. EldridgeBrittany N. EldridgeDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesMore by Brittany N. Eldridge,
- Han ZhangHan ZhangDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesSchool of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, ChinaMore by Han Zhang,
- Chengqiong MaoChengqiong MaoDepartment of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesMore by Chengqiong Mao,
- Yuanzeng MinYuanzeng MinDepartment of Chemistry, University of Science and Technology of China, Hefei 230000, Anhui, ChinaMore by Yuanzeng Min,
- Yao SunYao SunDepartment of Radiology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesMore by Yao Sun,
- Ravi Singh*Ravi Singh*E-mail: [email protected] (R.S.).Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesMore by Ravi Singh, and
- Xin Ming*Xin Ming*E-mail: [email protected] (X.M.).Department of Cancer Biology, Department of Biomedical Engineering, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, United StatesMore by Xin Ming
Abstract
P-Glycoprotein (Pgp)-medicated multidrug resistance (MDR) remains a formidable challenge to cancer therapy. As conventional approaches using small-molecule inhibitors failed in clinical development because of the lack of cancer specificity, we develop Pgp-targeted carbon nanotubes to achieve highly cancer-specific therapy through combining antibody-based cancer targeting and locoregional tumor ablation with photothermal therapy. Through a dense coating with phospholipid–poly(ethylene glycol), we have engineered multiwalled carbon nanotubes (MWCNTs) which show minimum nonspecific cell interactions and maximum intercellular diffusion. After chemically modifying with an anti-Pgp antibody, these MWCNTs showed highly Pgp-specific cellular uptake. Treatment of the targeted MWCNTs caused dramatic cytotoxicity in MDR cancer cells upon photoirradiation, whereas they did not cause any toxicity in the dark or phototoxicity toward normal cells that do not express Pgp. Because of excellent intratumor diffusion and Pgp-specific cellular uptake, the targeted MWCNTs produced strong phototoxicity in tumor spheroids of MDR cancer cells, a 3-D tumor model for studying tumor penetration and therapy. In conclusion, we have developed highly Pgp-specific MWCNTs that may provide an effective therapy for MDR cancers where other approaches have failed.
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- Shiv Kumar Prajapati, Akanksha Malaiya, Payal Kesharwani, Deeksha Soni, Aakanchha Jain. Biomedical applications and toxicities of carbon nanotubes. Drug and Chemical Toxicology 2020, 52 , 1-16. https://doi.org/10.1080/01480545.2019.1709492
- D. Gao, X. Guo, X. Zhang, S. Chen, Y. Wang, T. Chen, G. Huang, Y. Gao, Z. Tian, Z. Yang. Multifunctional phototheranostic nanomedicine for cancer imaging and treatment. Materials Today Bio 2020, 5 , 100035. https://doi.org/10.1016/j.mtbio.2019.100035
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- V.R. Raphey, T.K. Henna, K.P. Nivitha, P. Mufeedha, Chinnu Sabu, K. Pramod. Advanced biomedical applications of carbon nanotube. Materials Science and Engineering: C 2019, 100 , 616-630. https://doi.org/10.1016/j.msec.2019.03.043
- 铭 霍. Application and Toxicity of Carbon Nano-Tubes in Biomedicine. Advances in Material Chemistry 2019, 07 (01) , 1-7. https://doi.org/10.12677/AMC.2019.71001
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