PEGylated anticancer-carbon nanotubes complex targeting mitochondria of lung cancer cells

Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-...

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Vydané v:Nanotechnology Ročník 28; číslo 46; s. 465102
Hlavní autori: Kim, Sang-Woo, Kyung Lee, Yeon, Yeon Lee, Jong, Hee Hong, Jeong, Khang, Dongwoo
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: England 17.11.2017
Predmet:
A549 Cells
Biphenyl Compounds - chemistry
Biphenyl Compounds - pharmacology
Carcinoma, Non-Small-Cell Lung - drug therapy
Carcinoma, Non-Small-Cell Lung - metabolism
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Endosomes - chemistry
Humans
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Membrane Potential, Mitochondrial - drug effects
Mitochondria - drug effects
Mitochondria - metabolism
Nanotubes, Carbon - chemistry
Nitrophenols - chemistry
Nitrophenols - pharmacology
Piperazines - chemistry
Piperazines - pharmacology
Polyethylene Glycols - chemistry
Proto-Oncogene Proteins c-bcl-2 - metabolism
Reactive Oxygen Species - metabolism
Sulfonamides - chemistry
Sulfonamides - pharmacology
ISSN:1361-6528
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Popis
Shrnutí:Although activating apoptosis in cancer cells by targeting the mitochondria is an effective strategy for cancer therapy, insufficient targeting of the mitochondria in cancer cells restricts the availability in clinical treatment. Here, we report on a polyethylene glycol-coated carbon nanotube (CNT)-ABT737 nanodrug that improves the mitochondrial targeting of lung cancer cells. The polyethylene glycol-coated CNT-ABT737 nanodrug internalized into the early endosomes via macropinocytosis and clathrin-mediated endocytosis in advance of early endosomal escape and delivered into the mitochondria. Cytosol release of the nanodrug led to apoptosis of lung cancer cells by abruption of the mitochondrial membrane potential, inducing Bcl-2-mediated apoptosis and generating intracellular reactive oxygen species. As such, this study provides an effective strategy for increasing the anti-lung cancer efficacy by increasing mitochondria accumulation rate of cytosol released anticancer nanodrugs.
ISSN:1361-6528
DOI:10.1088/1361-6528/aa8c31