Nano-Biotechnology Key Lab of Hebei Province, Hebei Key Laboratory of Applied Chemistry, College of Environmental and Chemical Engineering, Yanshan University, Qinhuangdao, Hebei, Province 066000, People's Republic of China.
Qinhuangdao Biopha Biotechnology Co., Ltd, Qinhuangdao, Hebei Province 066000, People's Republic of China.
Biomed Mater. 2024 May 10;19(4). doi: 10.1088/1748-605X/ad46bb.
During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnOlayer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O) through the reaction between MnOand HOafter entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with Oin tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.
在恶性肿瘤治疗过程中，由于肿瘤细胞的缺氧环境，光动力疗法（PDT）疗效不佳，并且长时间的化疗会由于细胞膜上存在将药物向外运输的耐药蛋白，降低肿瘤细胞对化疗药物的敏感性。因此，我们报道了一种基于介孔硅包覆聚多巴胺（MSN@PDA）负载 PDT 增强剂 MnO、光敏剂吲哚菁绿（ICG）和化疗药物阿霉素（DOX）的纳米平台（命名为 DMPIM），以实现不同药物的顺序释放，增强恶性肿瘤的治疗效果。首先通过模板法合成 MSN，然后将 DOX 载入 MSN 的介孔通道中，并通过 PDA 涂层锁定。接下来，ICG 通过在 PDA 上的π-π堆积进行修饰，最后，MnO 层在 DOX@MSN@PDA-ICG@MnO 的表面上积累，实现了不同药物的正交装载和顺序释放。DMPIM 进入肿瘤细胞后，首先通过 MnO 和 HO 之间的反应产生氧（O），缓解肿瘤的缺氧环境，增强顺序释放的 ICG 的 PDT 效果。然后，ICG 在肿瘤组织中与 O 反应产生活性氧，促进药物的溶酶体逃逸和肿瘤细胞膜上 p-糖蛋白（p-gp）的失活。负载在 MSN 通道中的 DOX 在 ICG 释放后大约 8 小时才表现出增强的化疗效果。该药物递送系统实现了有效的顺序释放和多模式组合治疗，对恶性肿瘤达到了理想的治疗效果。这项工作为顺序药物释放提供了一种途径，推进了恶性肿瘤的治疗。
