期刊
CHINESE CHEMICAL LETTERS
卷 32, 期 2, 页码 729-734出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cclet.2020.08.035
关键词
Drug delivery system; Host-guest chemistry; Macrocyclic chemistry; Supramolecular chemotherapy; Supramolecular chemistry
资金
- National Natural Science Foundation of China [21871108]
- Jilin Province-University Cooperative Construction Project-Special Funds for New Materials [SXGJSF2017-3]
- Jilin University Talents Cultivation Program
By utilizing water-soluble macrocyclic hosts like CLT6 and CBpP6, this study successfully loaded the chemotherapy drug oxaliplatin, and achieved drug release through competitive binding, leading to enhanced cytotoxicity in cancer cells while reducing toxicity in normal cells, offering a new approach to reduce side effects of anticancer drugs.
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 subset of CLT6 and OxPt subset of 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/C6pP6 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 subset of CLT6 and OxPt subset of 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 (C) 2020 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
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