title: Polymer nanoparticle delivery of dichloroacetate and DACH-Pt to enhance antitumor efficacy and lower systemic toxicity.
abstract: Platinum agents can cause DNA damage and thus induce apoptosis of cancer cells, which has made them the backbone of cancer chemotherapy regimens. However, most cancers will develop drug resistance over the course of treatment. Meanwhile, most tumors meet energy needs largely by aerobic glycolysis (glycolysis in the presence of oxygen, called the Warburg effect), which is related to their resistance to apoptosis. Therefore, we have used a biodegradable polymer carrier to conjugate with DACH-Pt and dichloroacetate, a PDK inhibitor that can reverse the Warburg effect and derepress the resistance to apoptosis, thus sensitizing cancer cells to platinum. The as-prepared polymer-drug conjugates can be assembled into nanoparticles for effective delivery and better synergism. In vitro and in vivo studies revealed that the combination of polymer-DCA and polymer-DACH-Pt are much better than the free drugs administered simultaneously, in terms of both safety and antitumor efficacy.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. zehuawang@163.net.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.forename: Xiang
authors.initials: X
authors.lastname: Kang
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Yapei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lesan
authors.initials: L
authors.lastname: Yan
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
authors.forename: Zehua
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003999:Dichloroacetic Acid / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011108:Polymers; D010984:Platinum; C044245:1,2-diaminocyclohexaneplatinum II citrate; D003999:Dichloroacetic Acid