Polymer Nanoparticle Delivery of Dichloroacetate and DACH-Pt to enhance the antitumor efficacy and lower the systemic toxicity
Platinum agents can cause DNA damage and induce apoptosis to cancer cells, thus they became the backbone of cancer chemotherapy regimens, however, most cancers will develop drug resistance during the treatment.Meanwhile, most of the solid tumors meet energy needs largely by aerobic glycolysis, glycolysis in the presence of oxygen, called the Warburg effect, and Warburg effect is related to the resistance to apoptosis.Therefore, we use a biodegradable polymer carrier to conjugate with DACH-Pt and dichloroacetate (a PDK inhibitor which can reverse the Warburg effect to derepress the resistance to apoptosis, thus sensitize cancer cells to platinum), and 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 combined, in terms of both safety and antitumor efficay.
platinum dichloroacetate drug delivery Warburg effect synergism
Qiang Yang Jing Cai Si Sun Jing Guo Yapei Zhu Linjuan Xu Tao Li
Department of Obstetrics and Gynecology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China
国内会议
广州
英文
534-548
2015-09-10（万方平台首次上网日期，不代表论文的发表时间）