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Nanostructure of Functional Larotaxel Liposomes Decorated with Guanine‐Rich Quadruplex Nucleotide–Lipid Derivative for Treatment of Resistant Breast Cancer
Author(s) -
Li Xueqi,
Li Jianwei,
Xu Jiarui,
Chen Kun,
Zhang Zhan,
Duan Jialun,
Luo Qian,
Du Yafei,
Chen Songyue,
Xie Ying,
Lu Wanliang
Publication year - 2021
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202007391
Subject(s) - liposome , cancer cell , cancer research , nanomedicine , cancer , breast cancer , chemistry , pharmacology , biochemistry , biology , medicine , materials science , nanotechnology , nanoparticle
Abstract Breast cancer is the most common malignant disease in women all over the world and its chemotherapy outcome is restricted by multidrug resistance. Here, a nanostructure by functional larotaxel liposomes decorated with guanine‐rich quadruplex nucleotide‐lipid derivative for treatment of resistant breast cancer is developed. The studies are performed on the resistant breast cancer cells and the cancer‐bearing mice. The nucleotide–lipid derivative (DSPE‐PEG 2000 ‐C 6 ‐GT28nt) is synthesized by introducing a hydrophobic hexyl linkage between GT‐28nt (containing 17 guanines and 11 thymidines) and DSPE‐PEG 2000 ‐NHS, and is incorporated on the functional larotaxel liposomes for specific binding with nucleolin receptor on the resistant cancer cells. The studies demonstrate that the liposomes had long circulatory effect, targeted capability, and significant anticancer efficacy in resistant cancer‐bearing mice. The studies further reveal their action mechanism, consisting of blocking depolymerization of microtubules, arresting cell cycle, blocking JAK‐STAT signaling pathway, and inhibiting activity of antiapoptotic proteins. In conclusion, the functional larotaxel liposomes can be used for effective treatment of drug‐resistant breast cancer, and this study also offers a novel targeted nanomedicine based on nucleotide–lipid derivative.