Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People's Republic of China.
Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People's Republic of China.
Int J Nanomedicine. 2024 Jun 13;19:5837-5858. doi: 10.2147/IJN.S466042. eCollection 2024.
PURPOSE: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer. METHODS: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)-modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO@ICG NP. In this structure, the HMnO carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects. RESULTS: Mn can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility. CONCLUSION: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.
目的:光疗以其高选择性、副作用少、可控性强、协同增强联合治疗等特点,被广泛应用于宫颈癌等疾病的治疗。
方法:本研究以中空介孔二氧化锰为载体,构建带正电荷的聚(盐酸烯丙胺)修饰的纳米颗粒(NPs)。通过添加磷酸氢根离子产生抗衡离子聚集效应,将光敏剂吲哚菁绿(ICG)高效负载到 NP 中。采用 HeLa 细胞膜包封,得到最终的 M-HMnO@ICG NP。在这种结构中,HMnO 载体响应性降解,在肿瘤微环境中释放 ICG,自身产生 O2 对 ICG 介导的光动力治疗(PDT)进行敏化,并消耗 GSH 以扩大氧化应激治疗效果[化学动力学治疗(CDT)+PDT]。肿瘤组织中积累的 ICG 通过单激光照射发挥协同 PDT/光热治疗(PTT)作用,提高效率,减少副作用。细胞膜包封增加了纳米药物在肿瘤组织中的积累,并赋予了免疫逃逸能力。此外,PTT 引起的局部高温可以增强 CDT。该纳米粒子的这些特性使其能够充分实现 PTT/PDT/CDT 和靶向作用。
结果:Mn 可以作为磁共振成像剂来指导治疗,ICG 可用于光热和荧光成像。静脉注射后,M-HMnO@ICG 有效地在小鼠肿瘤部位积累;近红外荧光、磁共振和光热成像可验证体内激光治疗的最佳时机。在近红外光条件下,M-HMnO@ICG NPs 组的治疗效果最佳,表现出良好的生物相容性。
结论:本研究设计了一种纳米仿生递药系统,可改善缺氧,响应肿瘤微环境,高效负载 ICG,为宫颈癌的协同光疗和 CDT 提供了一种新的经济便捷的策略。
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