pH-Responsive supramolecular DOX-dimer based on cucurbit[8]uril for selective drug release |
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Affiliation: | 1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, SAR, China;2. Aix Marseille Univ, CNRS, ICR, Marseille, France |
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Abstract: | A supramolecular dimer of doxorubicin (DOX) was constructed via ternary host-guest interactions between cucurbit[8]uril (CB[8]) and tryptophan modified DOX (DOX-Trp, connected with an acid-labile bond) and we demonstrate for the first time that a supramolecular dimer of DOX can be formed upon homo-dimerization by CB[8], which may act as a stimuli pH-responsive, supramolecular DOX dimer prodrug system. This supramolecular DOX dimer transported DOX efficiently and selectively to cancer cells, thereby exhibiting significantly minimized cytotoxicity against noncancerous cells while maintaining effective cytotoxicity against cancer cells. Under this strategy, many other anticancer drugs could be chemically modified and loaded as a dimeric “ammunition” into CB[8] as supramolecular dimer prodrug systems (or a “jet fighter”) for improved cancer therapy. |
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Keywords: | Host-guest Cucurbit[8]uril pH-Responsive Prodrug Drug delivery |
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