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Templated Assembly of pH‐Labile Polymer‐Drug Particles for Intracellular Drug Delivery
Author(s) -
Cui Jiwei,
Yan Yan,
Wang Yajun,
Caruso Frank
Publication year - 2012
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201201191
Subject(s) - drug delivery , mesoporous silica , polymer , conjugate , materials science , cytotoxicity , methacrylic acid , doxorubicin , nanoparticle , drug carrier , biophysics , combinatorial chemistry , copolymer , chemistry , nanotechnology , organic chemistry , mesoporous material , biochemistry , medicine , mathematical analysis , mathematics , surgery , chemotherapy , in vitro , biology , catalysis
The preparation of pH‐labile polymer‐drug particles via mesoporous silica‐templated assembly for anticancer drug delivery into cancer cells is reported. The polymer‐drug conjugate is synthesized via thiol‐maleimide click chemistry using thiolated poly(methacrylic acid) (PMA SH ) and a pH‐labile doxorubicin (Dox) derivative. Drug‐loaded polymer particles that are stable under physiological conditions are obtained through infiltration of the conjugates into mesoporous silica particles, followed by cross‐linking the PMA SH chains, and subsequent removal of the porous silica templates. The encapsulated Dox is released from the particles through cleavage of the hydrazone bonds between Dox and PMA SH at endosomal/lysosomal pH. Cell viability assays show that the assembled PMA SH particles have negligible cytotoxicity to LIM1899 human colorectal cancer cells. In comparison, Dox‐loaded PMA SH particles cause significant cell death following internalization. The reported particles represent a novel and versatile class of stimuli‐responsive carriers for controlled drug delivery.