State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , PR China and.
Drug Deliv. 2015 Jan;22(1):136-43. doi: 10.3109/10717544.2013.870258. Epub 2013 Dec 20.
Differences in energy metabolism between tumor cells and normal cells offer an attractive avenue of research into drug targets for tumor therapy. The use of a metabolic modulator (sodium dichloroacetate, DCA), administered in situ, to reverse the "Warburg effect" of tumor cells has been demonstrated as an effective tumor therapy. Herein, DCA and diisopropylamine dichloroacetate (DADA) were incorporated separately into polylactide (PLA) electrospun mats and applied to C26 tumor-bearing mice via in situ administration. After 12 d of treatment, the tumor suppression rates of 75% and 84% were achieved in the DC group (treated with a DCA-loaded mat) and the DA group (treated with a DADA-loaded mat), respectively. With tolerable physiologic toxicity under high local concentration, the DA group showed a 95% tumor suppression rate without any recurrence after 15 d of therapy. The desirable therapeutic effects of these metabolic modulators should ascribe to the energy-central metabolism-targeting effects of DCA and DADA, which were demonstrated both in vitro and in vivo. Therefore, DCA- and DADA-loaded mats are the effective anti-cancer drugs dosages to discriminate between tumor cells and normal cells for minimizing systemic toxicity.
肿瘤细胞与正常细胞之间的能量代谢差异为肿瘤治疗的药物靶点研究提供了一个有吸引力的途径。使用代谢调节剂（二氯乙酸钠，DCA）原位给药来逆转肿瘤细胞的“沃伯格效应”已被证明是一种有效的肿瘤治疗方法。在此，DCA 和二异丙胺二氯乙酸（DADA）分别被掺入聚乳酸（PLA）电纺垫中，并通过原位给药应用于 C26 荷瘤小鼠。经过 12d 的治疗，DC 组（用负载 DCA 的垫子治疗）和 DA 组（用负载 DADA 的垫子治疗）的肿瘤抑制率分别达到 75%和 84%。DA 组在高局部浓度下具有可耐受的生理毒性，在 15d 的治疗后，肿瘤抑制率达到 95%，没有任何复发。这些代谢调节剂的理想治疗效果归因于 DCA 和 DADA 的能量中心代谢靶向作用，无论是在体外还是体内都得到了证实。因此，负载 DCA 和 DADA 的垫子是区分肿瘤细胞和正常细胞的有效抗癌药物剂量，可以最大程度地减少全身毒性。
