title: Poly(PEGA)-b-poly(L-lysine)-b-poly(L-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride.
abstract: A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine)-block-poly(L-histidine) [p(PEGA)30-b-p(Lys)25-b-p(His)n] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 μg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery.
authors.forename: Renjith P
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: Department of Biomedical Science and BK 21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School , 160 Baekseo-ro, Gwangju, 501-746, Republic of Korea.
authors.forename: Saji
authors.initials: S
authors.lastname: Uthaman
authors.forename: Johnson V
authors.initials: JV
authors.lastname: John
authors.forename: Hye Ri
authors.initials: HR
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and BK 21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School , 160 Baekseo-ro, Gwangju, 501-746, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.forename: Huiju
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and BK 21 PLUS Center for Creative Biomedical Scientists, Chonnam National University Medical School , 160 Baekseo-ro, Gwangju, 501-746, Republic of Korea.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.forename: Hongsuk
authors.initials: H
authors.lastname: Suh
authors.forename: Il
authors.initials: I
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006639:Histidine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D051379:Mice; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011107:Polylysine; C033223:polyhistidine; D011092:Polyethylene Glycols; D006639:Histidine; D004317:Doxorubicin
keywords: anticancer drug delivery; biocompatible polymer; nanovesicles; pH-responsive; self-assembly