Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the Fifth Affiliated Hospital and School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Adv Healthc Mater. 2023 Aug;12(20):e2203177. doi: 10.1002/adhm.202203177. Epub 2023 Apr 2.
Traditional starvation treatment strategies, which involve glucose oxidase and drug-induced thrombi, often suffer from aggravated tumor hypoxia and have failed to improve antitumor efficacy in combination with oxygen-dependent photodynamic therapy (PDT). Herein, glucose transporter 1 inhibitor genistein (Gen) and photosensitizer chlorin e6 (Ce6) are integrated to construct carrier-free self-assembled nanoparticles defined as GC NPs, for starvation therapy-amplified PDT of tumor. GC NPs with regular morphology and stability are screened out by component adjustment, while the function of each component is preserved. On the one hand, Gen released from GC NPs can cut off tumor glucose uptake by inhibiting the glucose transporter 1 to restrict tumor growth, achieving starvation therapy. On the other hand, they are able to decrease the amount of oxygen consumed by tumor respiration and amplify the therapeutic effect of PDT. In vitro and in vivo experiments verify the excellent synergistic antitumor therapeutic efficacy of GC NPs without any apparent toxicity. Moreover, fluorescence and photoacoustic imaging provide guidance for in vivo PDT, demonstrating the excellent tumor enrichment efficiency of GC NPs. It is believed that this starvation therapy-amplified PDT strategy by carrier-free self-assembled GC NPs holds promising clinical prospects.
传统的饥饿治疗策略，包括葡萄糖氧化酶和药物诱导的血栓，往往会加剧肿瘤缺氧，并未能改善与氧依赖的光动力疗法（PDT）联合的抗肿瘤疗效。在此，葡萄糖转运蛋白 1 抑制剂染料木黄酮（Gen）和光敏剂氯乙酮（Ce6）被整合到无载体自组装纳米颗粒中，定义为 GC NPs，用于肿瘤的饥饿治疗增强 PDT。通过成分调整筛选出形态和稳定性均规则的 GC NPs，同时保留了每个成分的功能。一方面，GC NPs 释放的 Gen 通过抑制葡萄糖转运蛋白 1 阻断肿瘤摄取葡萄糖，限制肿瘤生长，实现饥饿治疗。另一方面，它们能够减少肿瘤呼吸消耗的氧气量，并放大 PDT 的治疗效果。体外和体内实验验证了 GC NPs 具有优异的协同抗肿瘤治疗效果，且无明显毒性。此外，荧光和光声成像为体内 PDT 提供了指导，证明了 GC NPs 具有优异的肿瘤富集效率。相信这种无载体自组装 GC NPs 的饥饿治疗增强 PDT 策略具有广阔的临床前景。
