title: A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.
abstract: Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy.
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Hwa Seung
authors.initials: HS
authors.lastname: Han
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Minchang
authors.initials: M
authors.lastname: Lee
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: An
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Son
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Ko
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Hansang
authors.initials: H
authors.lastname: Lee
authors.affiliation: School of Medicine, Kyungpook National University, Daegu, 700-422, Republic of Korea.
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.affiliation: School of Medicine, Kyungpook National University, Daegu, 700-422, Republic of Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006863:Hydrogen-Ion Concentration; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; C014392:carboxymethyl dextran
keywords: carboxymethyl dextran; docetaxel; pH sensitive; polymeric conjugates