Yu Min, Xue Jian, Liu Nan, Ren Xiangling, Tan Longfei, Fu Changhui, Wu Qiong, Niu Meng, Zou Jingyu, Meng Xianwei
State Key Laboratory of Cryogenics Science and Technology, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China; Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China.
J Colloid Interface Sci. 2025 Nov;697:137979. doi: 10.1016/j.jcis.2025.137979. Epub 2025 May 23.
Glycolysis serves as the principal metabolic pathway through which tumor cells derive their energy. Targeting glycolysis to disrupt the energy supply at its origin presents a promising strategy for inhibiting tumor growth, recurrence, and metastasis. In this study, we developed a nanocomposite drug, ZIF-90@DOX@AP@PEG (ZDAP), utilizing zeolitic imidazole frameworks (ZIF-90) as carriers responsive to the tumor microenvironment (TME). This system co-delivers the glycolysis inhibitor apigenin (AP) alongside the chemotherapeutic agent doxorubicin (DOX), facilitating a triple-combination therapy approach for breast cancer treatment. ZIF-90 serves a dual role as a microwave (MW) sensitizer and as a responsive agent that degrades under TME-specific conditions, such as low pH and elevated adenosine triphosphate (ATP) levels, thereby facilitating controlled drug release. Experimental investigations, both in vitro and in vivo, have shown that the synergistic integration of MW hyperthermia, chemotherapy, and glycolysis inhibition substantially surpasses the effectiveness of individual therapies. These results highlight the potential of glycolysis inhibition to augment the efficacy of multimodal cancer treatments and propose a novel strategy for the integration of glycolytic inhibition with other therapeutic modalities.
糖酵解是肿瘤细胞获取能量的主要代谢途径。针对糖酵解在源头破坏能量供应，是抑制肿瘤生长、复发和转移的一种有前景的策略。在本研究中，我们开发了一种纳米复合药物ZIF-90@DOX@AP@PEG（ZDAP），利用沸石咪唑框架（ZIF-90）作为对肿瘤微环境（TME）有响应的载体。该系统将糖酵解抑制剂芹菜素（AP）与化疗药物阿霉素（DOX）共同递送，促进了用于乳腺癌治疗的三联疗法。ZIF-90起到双重作用，既是微波（MW）敏化剂，又是在低pH和三磷酸腺苷（ATP）水平升高等TME特异性条件下会降解的响应剂，从而促进药物的可控释放。体外和体内实验研究表明，MW热疗、化疗和糖酵解抑制的协同整合大大超过了单一疗法的效果。这些结果突出了糖酵解抑制增强多模式癌症治疗疗效的潜力，并提出了一种将糖酵解抑制与其他治疗方式相结合的新策略。
