School of Materials Science and Engineering, Institute of Nano and Biopolymeric Materials, Tongji University, Shanghai 201804, China.
Research Center for Translational Medicine at Shanghai East Hosptial, School of Life Science and Technology, Tongji University, Shanghai 20092, China.
ACS Appl Mater Interfaces. 2024 Jun 12;16(23):29902-29916. doi: 10.1021/acsami.4c04952. Epub 2024 May 29.
Metabolic rewiring, a dynamic metabolic phenotype switch, confers that tumors exist and proliferate after fitness (or preadaptation) in harsh environmental conditions. Glycolysis deprivation was considered to be a tumor's metabolic Achilles heel. However, metabolic configuration can flexibly retune the mitochondrial metabolic ability when glycolysis is scared, potentially resulting in more aggressive clones. To address the challenge of mitochondrial reprogramming, an antiglycolytic nanoparticle (GRPP NP) containing a novel mitochondrial-targeted reactive oxygen species (ROS) generator (diIR780) was prepared to hijack glucose and regulate mitochondria, thus completely eliminating tumorigenic energy sources. In this process, GRPP NPs@diIR780 can catalyze endogenous glucose, leading to significantly suppressed glycolysis. Moreover, diIR780 can be released and selectively accumulated around mitochondria to generate toxic ROS. These combined effects, in turn, can hamper mitochondrial metabolism pathways, which are crucial for driving tumor progression. This synchronous intervention strategy enables utter devastation of metabolic rewiring, providing a promising regiment to eradicate tumor lesions without recurrence.
代谢重编程是一种动态的代谢表型转换，使肿瘤在适应（或预先适应）恶劣环境条件后得以存在和增殖。糖酵解剥夺被认为是肿瘤的代谢阿喀琉斯之踵。然而，当糖酵解受到威胁时，代谢结构可以灵活地重新调整线粒体代谢能力，从而可能导致更具侵略性的克隆。为了解决线粒体重编程的挑战，制备了一种含有新型线粒体靶向活性氧（ROS）发生器（diIR780）的抗糖酵解纳米颗粒（GRPP NP），以劫持葡萄糖并调节线粒体，从而彻底消除致瘤性的能量来源。在这个过程中，GRPP NPs@diIR780 可以催化内源性葡萄糖，导致糖酵解显著受到抑制。此外，diIR780 可以被释放并选择性地在线粒体周围积累，以产生有毒的 ROS。这些综合效应反过来又会阻碍驱动肿瘤进展的线粒体代谢途径。这种同步干预策略可以彻底破坏代谢重编程，提供一种有前途的方案来消除肿瘤病变而不复发。
