title: Heparin-conjugated pluronic nanogels as multi-drug nanocarriers for combination chemotherapy.
abstract: Combination chemotherapy using more than two therapeutic agents with different modes of action is a promising strategy that can be used to enhance the therapeutic efficacy of cancer treatment, even though it is a complicated treatment modality. The aim of this study was to investigate how a novel multidrug nanocarrier is effective for combination chemotherapy in vitro and, more specifically, whether combined agents with different modes of action and physicochemical properties show synergistic cytotoxicity with the use of this nanocarrier. A heparin-Pluronic (Hep-Pr) nanogel encapsulating both paclitaxel and DNase was shown to be efficient for intracellular delivery with respect to size, encapsulation efficiency, and intracellular uptake/fates. As a result of these properties, a Hep-Pr nanogel combined with paclitaxel and DNase exhibited a dose-dependent synergistic cytotoxicity compared to single drug and free-drug treatments, whose combination indices were 0.93 and 0.45 at higher concentrations (250 and 500 μg/mL). Therefore, Hep-Pr nanogels have the potential to deliver multitherapeutic agents with different characteristics and thereby enhance the therapeutic efficacy of combination cancer chemotherapy.
authors.affiliation: Department of Molecular Science and Technology, Ajou University , 5 Wonchon, Yeongtong, Suwon, 443-749, Republic of Korea.
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Joung
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Jang
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Dong Keun
authors.initials: DK
authors.lastname: Han
authors.forename: Ki Dong
authors.initials: KD
authors.lastname: Park
mesh_terms: D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D005434:Flow Cytometry; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D000080385:Nanogels; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D006493:Heparin; D017239:Paclitaxel