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Efficient Encapsulation of β-Lapachone into Self-Immolative Polymer Nanoparticles for Cyclic Amplification of Intracellular Reactive Oxygen Species Stress
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-12 , DOI: 10.1021/acsnano.4c09232 Lingxiao Guo 1 , Zexuan Ding 1 , Jinming Hu 1 , Shiyong Liu 1
ACS Nano ( IF 15.8 ) Pub Date : 2024-09-12 , DOI: 10.1021/acsnano.4c09232 Lingxiao Guo 1 , Zexuan Ding 1 , Jinming Hu 1 , Shiyong Liu 1
Affiliation
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The selective upregulation of intracellular oxidative stress in cancer cells presents a promising approach for effective cancer treatment. In this study, we report the integration of enzyme catalytic amplification and chemical amplification reactions in β-lapachone (Lap)-loaded micellar nanoparticles (NPs), which are self-assembled from reactive oxygen species (ROS)-responsive self-immolative polymers (SIPs). This integration enables cyclic amplification of intracellular oxidative stress in cancer cells. Specifically, we have developed ROS-responsive SIPs with phenylboronic ester triggering motifs and hexafluoroisopropanol moieties in the side chains, significantly enhancing Lap loading efficiency (98%) and loading capacity (33%) through multiple noncovalent interactions. Upon ROS activation in tumor cells, the Lap-loaded micellar NPs disassemble, releasing Lap and generating additional ROS via enzyme catalytic amplification. This process elevates intracellular oxidative stress and triggers polymer depolymerization in a positive feedback loop. Furthermore, the degradation of SIPs via chemical amplification produces azaquinone methide intermediates, which consume intracellular thiol-related substrates, disrupt intracellular redox hemostasis, further intensify oxidative stress, and promote cancer cell apoptosis. This work introduces a strategy to enhance intracellular oxidative stress by combining enzymatic and chemical amplification reactions, providing a potential pathway for the development of highly efficient anticancer agents.
中文翻译：
将 β-Lapachone 有效封装到自焚聚合物纳米颗粒中，用于循环放大细胞内活性氧应激
癌细胞中细胞内氧化应激的选择性上调为有效的癌症治疗提供了一种有前景的方法。在这项研究中，我们报道了负载β-拉帕酮（Lap）的胶束纳米粒子（NP）中酶催化放大和化学放大反应的整合，这些纳米粒子是由活性氧（ROS）响应的自毁聚合物自组装而成。 SIP）。这种整合使得癌细胞中细胞内氧化应激循环放大。具体来说，我们开发了侧链中具有苯基硼酸酯触发基序和六氟异丙醇部分的 ROS 响应 SIP，通过多种非共价相互作用显着提高 Lap 负载效率 (98%) 和负载容量 (33%)。当肿瘤细胞中 ROS 激活时，负载 Lap 的胶束纳米粒子分解，释放 Lap 并通过酶催化放大产生额外的 ROS。该过程会升高细胞内氧化应激并在正反馈回路中触发聚合物解聚。此外，SIP通过化学扩增降解产生氮杂醌甲基化物中间体，其消耗细胞内硫醇相关底物，破坏细胞内氧化还原止血，进一步加剧氧化应激，促进癌细胞凋亡。这项工作引入了一种通过结合酶促和化学放大反应来增强细胞内氧化应激的策略，为开发高效抗癌药物提供了潜在途径。
更新日期：2024-09-12
中文翻译：
将 β-Lapachone 有效封装到自焚聚合物纳米颗粒中，用于循环放大细胞内活性氧应激
癌细胞中细胞内氧化应激的选择性上调为有效的癌症治疗提供了一种有前景的方法。在这项研究中，我们报道了负载β-拉帕酮（Lap）的胶束纳米粒子（NP）中酶催化放大和化学放大反应的整合，这些纳米粒子是由活性氧（ROS）响应的自毁聚合物自组装而成。 SIP）。这种整合使得癌细胞中细胞内氧化应激循环放大。具体来说，我们开发了侧链中具有苯基硼酸酯触发基序和六氟异丙醇部分的 ROS 响应 SIP，通过多种非共价相互作用显着提高 Lap 负载效率 (98%) 和负载容量 (33%)。当肿瘤细胞中 ROS 激活时，负载 Lap 的胶束纳米粒子分解，释放 Lap 并通过酶催化放大产生额外的 ROS。该过程会升高细胞内氧化应激并在正反馈回路中触发聚合物解聚。此外，SIP通过化学扩增降解产生氮杂醌甲基化物中间体，其消耗细胞内硫醇相关底物，破坏细胞内氧化还原止血，进一步加剧氧化应激，促进癌细胞凋亡。这项工作引入了一种通过结合酶促和化学放大反应来增强细胞内氧化应激的策略，为开发高效抗癌药物提供了潜在途径。
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