State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin, Changchun, 130022, China.
University of Science and Technology of China, Anhui, Hefei, 230026, China.
Angew Chem Int Ed Engl. 2024 Mar 18;63(12):e202317304. doi: 10.1002/anie.202317304. Epub 2024 Feb 15.
Pyroptosis is an effective anti-tumor strategy. However, monometallic pyroptosis biotuners have not been explored until now. Here, we discover for the first time that biodegradable monometallic Al can act as a pyroptosis biotuner for tumor therapy. pH-sensitive Al nanoparticles (Al@P) are obtained by equipping polyethylene glycol-b-(poly(methyl methacrylate)-co-poly(4-vinylpyridine), which can exert their effect at the tumor site without affecting normal cells. The H and Al release by Al@P in the acidic environment of tumors disrupts the redox balance and ionic homeostasis in tumor cells, thus generating large amounts of reactive oxygen species (ROS), leading to caspase-1 activation, gasdermin D cleavage, and IL-1β/LDH release, which induces canonical pyroptotic death. Meanwhile, the prodrug Doxorubicin (Pro-DOX) is successfully loaded onto Al@P (Al@P-P) and can be activated by ROS to release DOX in the tumor cells, thus further improving the tumor-killing efficiency. Ultimately, Al@P-P is degradable and exhibits efficient tumor inhibition.
细胞焦亡是一种有效的抗肿瘤策略。然而，直到现在，人们才开始探索单金属细胞焦亡生物调节剂。在这里，我们首次发现可生物降解的单金属铝可以作为肿瘤治疗的细胞焦亡生物调节剂。通过在聚乙二醇-b-（聚（甲基丙烯酸甲酯）-co-聚（4-乙烯基吡啶）上装备，得到了对 pH 敏感的铝纳米颗粒（Al@P），它可以在肿瘤部位发挥作用，而不会影响正常细胞。Al@P 在肿瘤酸性环境中释放的 H 和 Al 破坏了肿瘤细胞的氧化还原平衡和离子内稳态，从而产生大量的活性氧（ROS），导致半胱氨酸天冬氨酸蛋白酶-1 激活、Gasdermin D 切割和 IL-1β/LDH 释放，从而诱导经典的细胞焦亡死亡。同时，阿霉素前药（Pro-DOX）成功负载到 Al@P（Al@P-P）上，并可被 ROS 激活，在肿瘤细胞中释放 DOX，从而进一步提高肿瘤杀伤效率。最终，Al@P-P 是可降解的，并表现出高效的肿瘤抑制作用。
