Journal
MACROMOLECULAR RAPID COMMUNICATIONS
Volume 39, Issue 20, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/marc.201800139
Keywords
drug delivery; micelles; pH-sensitive; reduction-sensitive; shell-sheddable
Categories
Funding
- National Natural Science Foundation of China [51503013, 51390481, 21774008, 81472412]
- China Postdoctoral Science Foundation [2015M570919]
- Initiative Project of Beijing Hospital [BJ-2018-026]
- Fundamental Research Funds for the Central Universities [ZY1519, XK1701]
- Ministry of Finance
- Ministry of Education of PRC for BUCT
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Poly(ethylene glycol) (PEG) shell-sheddable micelles are proved to be effective tools for rapid intracellular drug delivery. However, some adverse factors, such as the potential immunogenicity and the accelerated blood clearance, might be accompanied with the traditional PEG sheddable micelles. Here, a poly(N-2-hydroxypropyl methacrylamide) (PHPMA) sheddable block copolymer containing disulfide bonds on the main chain is prepared to form pH- and reduction-dual-responsive micelles. The most optimal synthetic route of the block copolymer is selected from three potential pathways. Doxorubicin is loaded via an acid-labile hydrazone bond to achieve high drug loading content and to prevent premature drug release. As expected, as-prepared shell-sheddable micelles exhibit faster intracellular drug release and more satisfactory in vitro anticancer efficacy than the nonsheddable counterpart did. This design provides a feasible guideline for the efficient synthesis of similar shell-sheddable micelles consisting of PHPMA coatings.
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