奥沙利铂
细胞毒性
化疗
药品
化学
药物输送
超分子化学
药理学
组合化学
癌症
癌症研究
生物化学
体外
医学
内科学
有机化学
分子
结直肠癌
作者
Jie Yang,Dihua Dai,Lu‐Fang Ma,Ying‐Wei Yang
标识
DOI:10.1016/j.cclet.2020.08.035
摘要
Smart strategies that can decrease the side effect and enhance the therapeutic efficacy of chemotherapy are in urgent need to meet the special demands of cancer therapy. Herein, two water-soluble macrocyclic hosts, i.e., a carboxylated leaning tower[6]arene (CLT6) and a carboxylated [2]biphenyl-extended pillar[6]arene (CBpP6), are used to load chemotherapy drug oxaliplatin (OxPt) by forming inclusion complexes (OxPt⊂CLT6 and OxPt⊂CBpP6) through host-guest interactions. Interestingly, OxPt can be released from the macrocyclic cavities of these drug delivery systems (DDSs) via the competitive binding effect of spermine (SPM) because of the stronger binding abilities of CLT6/CBpP6 toward SPM as compared with OxPt, leading to enhanced cytotoxicity on SPM-overexpressed cancer cells, such as breast cancer MCF-7 cells. Moreover, compared to free OxPt, due to the low concentration of SPM in normal cells, OxPt⊂CLT6 and OxPt⊂CBpP6 demonstrated a decreased cytotoxicity on liver L02 cells, which is beneficial for reducing the side effect of anticancer drug during chemotherapy. Such a strategy might be extended to other antitumor drugs and water-soluble macrocycles with suitable cavity sizes to achieve controllable drug delivery and enhanced anticancer ability in supramolecular chemotherapy
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