Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and molecular imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
West China-Washington Mitochondria and Metabolism Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Adv Mater. 2020 Apr;32(14):e1907490. doi: 10.1002/adma.201907490. Epub 2020 Feb 21.
Metabolic demand of cancer is quite unique compared to normal tissues and this is an emerging hallmark of cancer, which brings a potential opportunity to discover drugs that target cancer cell metabolism. Herein, the development of a dendronized pyropheophorbide a (Ppa)-conjugated polymer (DPP) is reported, and a linear Ppa-conjugated polymer (LPP) is reported as a control. DPP is found to disturb cellular metabolism including increased energy depletion, dysfunctional H regulation, and decreased antioxidation, resulting in deficiency in protecting cells from stresses. These vulnerable cells are subjected to photodynamic therapy (PDT) treatment in the presence of DPP, resulting in attenuated cancer cell growth and eventually cell death. The in vivo anticancer efficacy is also ascribed to significantly prolonged blood circulation and enhanced tumor accumulation of DPP due to its unique molecular structure. This study presents a new platform using dendronized polymers for tumor suppression by targeting cancer cell metabolism.
与正常组织相比，癌症的代谢需求非常独特，这是癌症的一个新的标志特征，为发现针对癌细胞代谢的药物提供了潜在的机会。本文报道了一种树状焦脱镁叶绿酸 a（Ppa）接枝聚合物（DPP）的开发，并报道了一种线性 Ppa 接枝聚合物（LPP）作为对照。研究发现 DPP 会干扰细胞代谢，包括能量耗竭增加、H 调节功能障碍和抗氧化能力降低，从而导致细胞无法抵御应激。在 DPP 的存在下，这些脆弱的细胞接受光动力治疗（PDT），导致癌细胞生长减弱，最终细胞死亡。由于其独特的分子结构，DPP 还具有显著延长血液循环和增强肿瘤积累的体内抗癌功效。本研究提出了一种使用树状聚合物通过靶向癌细胞代谢来抑制肿瘤的新平台。
