title: Localized Co-delivery of Doxorubicin, Cisplatin, and Methotrexate by Thermosensitive Hydrogels for Enhanced Osteosarcoma Treatment.
abstract: Localized cancer treatments with combination drugs have recently emerged as crucial approaches for effective inhibition of tumor growth and reoccurrence. In this study, we present a new strategy for the osteosarcoma treatment by localized co-delivery of multiple drugs, including doxorubicin (DOX), cisplatin (CDDP) and methotraxate (MTX), using thermosensitive PLGA-PEG-PLGA hydrogels. The release profiles of the drugs from the hydrogels were investigated in vitro. It was found that the multidrug coloaded hydrogels exhibited synergistic effects on cytotoxicity against osteosarcoma Saos-2 and MG-63 cells in vitro. After a single peritumoral injection of the drug-loaded hydrogels into nude mice bearing human osteosarcoma Saos-2 xenografts, the hydrogels coloaded with DOX, CDDP, and MTX displayed the highest tumor suppression efficacy in vivo for up to 16 days, as well as led to enhanced tumor apoptosis and increased regulation of the expressions of apoptosis-related genes. Moreover, the monitoring on the mice body change and the ex vivo histological analysis of the key organs indicated that the localized treatments caused less systemic toxicity and no obvious damage to the normal organs. Therefore, the approach of localized co-delivery of DOX, CDDP, and MTX by the thermosensitive hydrogels may be a promising approach for enhanced osteosarcoma treatment.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.|Department of Orthopaedics, The First Hospital of Jilin University , Changchun 130021, People's Republic of China.
authors.forename: Hecheng
authors.initials: H
authors.lastname: Ma
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Chaoliang
authors.initials: C
authors.lastname: He
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Yilong
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Orthopaedics, The First Hospital of Jilin University , Changchun 130021, People's Republic of China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, The First Hospital of Jilin University , Changchun 130021, People's Republic of China.
authors.forename: Junting
authors.initials: J
authors.lastname: Zang
authors.affiliation: Department of Orthopaedics, The First Hospital of Jilin University , Changchun 130021, People's Republic of China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun 130022, People's Republic of China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008727:Methotrexate / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D020100:Hydrogels; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate
keywords: combination therapy; injectable hydrogels; localized delivery; multidrug co-delivery; osteosarcoma treatment; synergistic therapy