Immobilization and intracellular delivery of an anticancer drug using mussel-inspired polydopamine capsules.
We report a facile approach to immobilize pH-cleavable polymer-drug conjugates in mussel-inspired polydopamine (PDA) capsules for intracellular drug delivery. Our design takes advantage of the facile PDA coating to form capsules, the chemical reactivity of PDA films, and the acid-labile groups in polymer side chains for sustained pH-induced drug release. The anticancer drug doxorubicin (Dox) was conjugated to thiolated poly(methacrylic acid) (PMA(SH)) with a pH-cleavable hydrazone bond, and then immobilized in PDA capsules via robust thiol-catechol reactions between the polymer-drug conjugate and capsule walls. The loaded Dox showed limited release at physiological pH but significant release (over 85%) at endosomal/lysosomal pH. Cell viability assays showed that Dox-loaded PDA capsules enhanced the efficacy of eradicating HeLa cancer cells compared with free drug under the same assay conditions. The reported method provides a new platform for the application of stimuli-responsive PDA capsules as drug delivery systems.
Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
Jiwei
J
Cui
Yan
Y
Yan
Georgina K
GK
Such
Kang
K
Liang
Christopher J
CJ
Ochs
Almar
A
Postma
Frank
F
Caruso
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D049872:Bivalvia; D002214:Capsules; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D002214:Capsules; D004337:Drug Carriers; D007211:Indoles; D011108:Polymers; D011109:Polymethacrylic Acids; C568283:polydopamine; D004317:Doxorubicin