Overcoming multidrug-resistant lung cancer by mitochondrial-associated ATP inhibition using nanodrugs

Journal of Nanobiotechnology

Research

Kwai Han Yoo¹  Gyu-Ho Lee²  Jun-Young Park³  Dongwoo Khang⁴ 

[1] Department of Internal Medicine, Gachon University Gil Medical Center, College of Medicine, 21565, Incheon, South Korea;Department of Physiology, College of Medicine, Gachon University, 21999, Incheon, South Korea;Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 21999, Incheon, South Korea;Department of Health Sciences and Technology, GAIHST, Gachon University, 21999, Incheon, South Korea;Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 21999, Incheon, South Korea;Department of Health Sciences and Technology, GAIHST, Gachon University, 21999, Incheon, South Korea;Department of Physiology, College of Medicine, Gachon University, 21999, Incheon, South Korea;

关键词: Carbon nanotube;    Doxorubicin;    Endosomal escape;    Multidrug resistant cell;    Small cell lung cancer;    Mitochondrial damage;   

DOI  :  10.1186/s12951-023-01768-8

 received in 2022-07-22, accepted in 2023-01-03,  发布年份 2023

来源: Springer

【 摘 要 】

Despite the development of therapeutic modalities to treat cancer, multidrug resistance (MDR) and incomplete destruction of deeply embedded lung tumors remain long-standing problems responsible for tumor recurrence and low survival rates. Therefore, developing therapeutic approaches to treat MDR tumors is necessary. In this study, nanodrugs with enhanced intracellular drug internalization were identified by the covalent bonding of carbon nanotubes of a specific nano size and doxorubicin (DOX). In addition, carbon nanotube conjugated DOX (CNT-DOX) sustained in the intracellular environment in multidrug-resistant tumor cells for a long time causes mitochondrial damage, suppresses ATP production, and results in the effective therapeutic effect of drug-resistant tumors. This study identified that H69AR lung cancer cells, an adriamycin (DOX) drug-resistant tumor cell line, did not activate drug resistance function on designed nano-anticancer drugs with a specific nano size. In summary, this study identified that the specific size of the nanodrug in combination with DOX overcame multidrug-resistant tumors by inducing selective accumulation in tumor cells and inhibiting ATP by mitochondrial damage.

【 授权许可】

CC BY   
© The Author(s) 2023

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