Ganapathy-Kanniappan Shanmugasundaram
a Johns Hopkins University School of Medicine, Department of Radiology & Radiological Sciences , 600 N Wolfe Street, Blalock 340, Baltimore, MD 21287, USA +1 41 05 02 62 28 ;
Expert Opin Ther Targets. 2016;20(1):1-5. doi: 10.1517/14728222.2016.1093114. Epub 2015 Sep 30.
Metabolic reprogramming is one of the hallmarks of cancer. Altered metabolism in cancer cells is exemplified by enhanced glucose utilization, a biochemical signature that is clinically exploited for cancer diagnosis using positron-emission tomography and computed tomography imaging. Accordingly, disrupting the glucose metabolism of cancer cells has been contemplated as a potential therapeutic strategy against cancer. Experimental evidences indicate that targeting glucose metabolism by inhibition of glycolysis or oxidative phosphorylation promotes anticancer effects. Yet, successful clinical translation of antimetabolites or energy blockers to treat cancer remains a challenge, primarily due to lack of efficacy and/or systemic toxicity. Recently, using nanotechnology, Marrache and Dhar have documented the feasibility of delivering a glycolytic inhibitor through triphenylphosphonium (TPP), a mitotropic agent that selectively targets mitochondria based on membrane potential. Furthermore, by utilizing gold nanoparticles the investigators also demonstrated the potential for simultaneous induction of photothermal therapy, thus facilitating an additional line of attack on cancer cells. The report establishes that specific inhibition of tumor glycolysis is achievable through TPP-dependent selective targeting of cancer cells. This nanotechnological approach involving TPP-guided selective delivery of an antiglycolytic agent complemented with photothermal therapy provides a new window of opportunity for effective and specific targeting of tumor glycolysis.
代谢重编程是癌症的标志之一。癌细胞代谢改变的一个例证是葡萄糖利用率提高，这是一种生化特征，临床上可利用正电子发射断层扫描和计算机断层扫描成像来进行癌症诊断。因此，破坏癌细胞的葡萄糖代谢已被视为一种潜在的抗癌治疗策略。实验证据表明，通过抑制糖酵解或氧化磷酸化来靶向葡萄糖代谢可促进抗癌作用。然而，抗代谢物或能量阻断剂在癌症治疗中的成功临床转化仍然是一个挑战，主要是由于缺乏疗效和/或全身毒性。最近，马拉切和达尔利用纳米技术证明了通过三苯基膦（TPP）递送糖酵解抑制剂的可行性，TPP是一种基于膜电位选择性靶向线粒体的亲线粒体剂。此外，通过利用金纳米颗粒，研究人员还证明了同时诱导光热疗法的潜力，从而为攻击癌细胞提供了额外的途径。该报告证实，通过TPP依赖的癌细胞选择性靶向可实现对肿瘤糖酵解的特异性抑制。这种涉及TPP引导的抗糖酵解剂选择性递送并辅以光热疗法的纳米技术方法为有效和特异性靶向肿瘤糖酵解提供了新的机会窗口。
