Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai 264003, People's Republic of China.
Science Fund of Shandong Laboratory of Advanced Materials and Green Manufacturing at Yantai, Yantai 264000, People's Republic of China.
ACS Appl Bio Mater. 2023 Nov 20;6(11):4998-5008. doi: 10.1021/acsabm.3c00678. Epub 2023 Oct 25.
Sonodynamic therapy (SDT) and chemotherapy have received great attention as effective methods for tumor treatment. However, the inherent hypoxia of the tumor greatly hinders its therapeutic efficacy. In this work, a tumor microenvironment-responsive biodegradable nanoplatform SiO-MnO-PEG-Ce6&DOX (designated as SMPC&D) is fabricated by encapsulating manganese oxide (MnO) into silica nanoparticles and anchoring poly(ethylene glycol) (PEG) onto the surface for tumor hypoxia relief and delivery, then loaded with sonosensitizer Chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) for hypoxic tumor treatment. We evaluated the physicochemical properties of SMPC&D nanoparticles and the tumor therapeutic effects of chemotherapy and SDT under ultrasound stimulation and . After endocytosis by tumor cells, highly expressed glutathione (GSH) triggers biodegradation of the nanoplatform and MnO catalyzes hydrogen peroxide (HO) to generate oxygen (O), thereby alleviating tumor hypoxia. Depleting GSH and self-supplying O effectively improve the SDT efficiency both and . Ultrasonic stimulation promoted the release and cellular uptake of chemotherapy drugs. In addition, the relieved hypoxia reduced the efflux of chemotherapy drugs by downregulating the expression of the P-gp protein, which jointly improved the effect of chemotherapy. This study demonstrates that the degradable SMPC&D as a therapeutic agent can achieve efficient chemotherapy and SDT synergistic therapy for hypoxic tumors.
声动力学疗法（SDT）和化学疗法作为肿瘤治疗的有效方法受到了极大关注。然而，肿瘤的固有缺氧极大地阻碍了其治疗效果。在这项工作中，通过将氧化锰（MnO）封装到硅纳米颗粒中，并将聚乙二醇（PEG）锚定在表面上，制备了一种肿瘤微环境响应性可生物降解纳米平台 SiO-MnO-PEG-Ce6&DOX（命名为 SMPC&D），用于缓解肿瘤缺氧和递送，然后负载声敏剂 Chlorin e6（Ce6）和化疗药物阿霉素（DOX）用于缺氧肿瘤治疗。我们评估了 SMPC&D 纳米颗粒的物理化学性质以及在超声刺激下的化疗和 SDT 的肿瘤治疗效果。纳米平台的生物降解和 MnO 催化过氧化氢（HO）生成氧气（O），从而缓解肿瘤缺氧，这是通过肿瘤细胞内吞后，高表达的谷胱甘肽（GSH）触发的。耗竭 GSH 和自供应 O 有效地提高了 SDT 效率。超声刺激促进了化疗药物的释放和细胞摄取。此外，缓解的缺氧通过下调 P-糖蛋白（P-gp）蛋白的表达减少了化疗药物的外排，从而共同提高了化疗效果。本研究表明，可降解的 SMPC&D 作为治疗剂可以实现缺氧肿瘤的高效化疗和 SDT 协同治疗。
