Distinct CPT-induced deaths in lung cancer cells caused by clathrin-mediated internalization of CP micelles

Nanoscale
Yu-Sheng LiuLi-Fang Wang

Abstract

We previously synthesized a chondroitin sulfate-graft-poly(ε-caprolactone) copolymer (H-CP) with a high content of poly(ε-caprolactone) (18.7 mol%), which self-assembled in water into a rod-like micelle to encapsulate hydrophobic camptothecin (CPT) in the core (micelle/CPT) for tumor-targeted drug delivery. As a result of the recognition of the micelle by CD44, the micelle/CPT entered CRL-5802 cells efficiently and released CPT efficaciously, resulting in higher tumor suppression than commercial CPT-11. In this study, H1299 cells were found to have a higher CD44 expression than CRL-5802 cells. However, the lower CD44-expressing CRL-5802 cells had a higher percentage of cell death and higher cellular uptake of the micelle/CPT than the higher CD44-expressing H1299 cells. Examination of the internalization pathway of the micelle/CPT in the presence of different endocytic chemical inhibitors showed that the CRL-5802 cells involved clathrin-mediated endocytosis, which was not found in the H1299 cells. Analysis of the cell cycle of the two cell lines exposed to the micelle/CPT revealed that the CRL-5802 cells arrested mainly in the S phase and the H1299 cells arrested mainly in the G2-M phase. A consistent result was also found in th...Continue Reading

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Citations

Jan 11, 2017·ACS Applied Materials & Interfaces·Lei ZhangShaobing Zhou
Dec 29, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Pablo Botella, Eva Rivero-Buceta
Nov 13, 2020·International Journal of Nanomedicine·Ming-Fong TsaiLi-Fang Wang
Apr 30, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Long Wang, Chengcheng Niu

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