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- Title
Shell‐Sheddable Poly(N‐2‐hydroxypropyl methacrylamide) Polymeric Micelles for Dual‐Sensitive Release of Doxorubicin.
- Authors
Zhang, Jiajing; Tang, Hao; Shen, Yi; Yu, Qingsong; Gan, Zhihua
- Abstract
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. The pH and reduction‐dual‐responsive poly(N‐2‐hydroxypropyl methacrylamide) shell‐sheddable micelles are fabricated with the combination of reversible addition‐fragmentation chain transfer, atom transfer radical polymerization, and postpolymerization modification technique. The loaded doxorubicin can be rapidly released under acidic and reducting stimuli inside cancer cells. Greater in vitro anticancer efficacy is observed for as‐prepared dual‐responsive micelle than the mono‐responsive micelle.
- Subjects
MICELLES; DOXORUBICIN; POLYETHYLENE glycol; IMMUNOGENETICS; BLOCK copolymers
- Publication
Macromolecular Rapid Communications, 2018, Vol 39, Issue 20, pN.PAG
- ISSN
1022-1336
- Publication type
Article
- DOI
10.1002/marc.201800139