期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 27, 页码 17109-17117出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b04247
关键词
self-assembly; polymer-drug conjugate; pH response; charge-conversion; controlled release
资金
- National Natural Science Foundation of China [51373142, 51403176, 51541307]
- Scientific and Technological Innovation Platform of Fujian Province [2014H2006]
- Fundamental Research Funds for the Central Universities [20720140516]
- National Science and Technology Ministry [2014BAF08B03]
To precisely deliver drug molecules at a targeted site and in a controllable manner, there has been great interest in designing a synergistical drug delivery system that can achieve both surface charge-conversion and controlled release of a drug in response to different stimuli. Here we outline a simple method to construct an intelligent drug carrier, which can respond to two different pH values, therefore achieving charge conversion and chemical-bond-cleavage-induced drug release in a stepwise fashion. This drug carrier comes from the self-assembly of a block copolymer-DOX conjugate synthesized through a Schiff base reaction between poly(2-(diisopropylamino)ethyl methacrylate-b-poly-(4-formylphenyl methacrylate-co-polyethylene glycol mono methyl ether methacrylate) (PDPA-b-P(FPMA-co-OEGMA)) and DOX. The surface charge of the BCP-DOX micelles reversed from negative to positive when encountering a weakly acidic environment due to the protonation of PDPA segments. In vitro cellular uptake measurement shows that the cellular uptake and internalisation of the BCP-DOX micelles can be significantly enhanced at pH similar to 6.5. Moreover, this drug carrier exhibits a pH-dependent drug release owing to the cleavage of the imine bond at pH < 5.5. With this dual-pH responsive feature, these micelles may have the ability to precisely deliver DOX to the cancer cells.
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