交变磁场响应的磁性介孔纳米体系用于乏氧肿瘤自由基治疗研究

Anticancer modalities based on reactive oxygen species, including photodynamic therapy and radiotherapy, have emerged as promising treatments in the clinic. However, the generation of reactive oxygen species is highly oxygen-dependent, tumor hypoxia greatly lowers the therapeutic efficacy of these treatments. Therefore, oxygen-irrelevant free-radical therapy provides a new idea for hypoxic tumor treatment. Herein, this project presents an alternating magnetic field responsive nanosystem Mag@DMSN-AMHP/Cy5.5 for magnetic hyperthermia effects enhanced free-radical therapy of hypoxic tumors. Upon actuation by an alternating magnetic field, the magnetic hyperthermia effects could induce the controllable release of free radicals. Improved therapeutic efficacy will be achieved by synergistic combination of free-radical therapy and magnetic hyperthermia therapy. Additionally, the generation of free radicals could be monitored by real-time fluorescence imaging. Furthermore, the composition and microstructure of the nanosystem will be controlled, and their structure parameters will be optimized. Their in vitro and in vivo biocompatibility will be comprehensively evaluated to guarantee further clinical translation. The in vivo investigation will demonstrate the therapeutic efficiency and mechanism of Mag@DMSN-AMHP/Cy5.5 as a multifunctional agent for magnetic hyperthermia effects enhanced free-radical therapy of hypoxic tumors. This research provides a new strategy to realize the therapeutic efficiency and biosafety issues of hypoxic tumor therapy based on nano-biotechnology.

基于活性氧的抗肿瘤治疗方法，包括光动力学疗法和放射疗法，有望应用于临床癌症的治疗。然而，由于活性氧自由基的产生高度依赖于氧气，肿瘤微环境乏氧极大地降低了这些治疗手段的效率。因此，不依赖于氧气产生的自由基治疗将为乏氧肿瘤高效治疗提供了一种新思路。基于此，本项目提出了一种交变磁场响应的磁性介孔纳米体系Mag@DMSN-AMHP/Cy5.5用于磁热效应增强乏氧肿瘤的自由基治疗。在外加交变磁场的作用下，纳米体系产生的磁热效应将会促进不依赖于氧气产生的自由基的可控释放，通过协同自由基治疗和磁热疗，实现对乏氧肿瘤的高效治疗。此外，荧光成像能够实时地监测自由基的产生。本项目将系统地调控纳米体系的微观结构和组成，优化其性能，评估其安全性，并采用动物肿瘤模型考察其对乏氧肿瘤的治疗效果，揭示磁热效应增强乏氧肿瘤自由基治疗的作用机制。该研究将为基于纳米生物技术提高乏氧肿瘤治疗效率和安全性提供了一种新策略。

基于活性氧自由基的抗肿瘤治疗手段有望应用于临床肿瘤的治疗。由于活性氧自由基的产生依赖肿瘤微环境的氧气含量，肿瘤微环境乏氧严重地降低了这些治疗手段的治疗效率。基于此，本项目开发了一种交变磁场响应的磁性介孔纳米体系Mag@MSNs@AIPH用于磁热效应增强乏氧肿瘤的自由基治疗。本项目通过系统地精确地调控构筑纳米体系的微观结构、组成成分和关键参数，优化其磁热和产生活性氧自由基的性能，评估其生物安全性。在外加交变磁场的作用下，所构筑的纳米体系产生的磁热效应促进不依赖氧气的自由基的可控释放，通过协同磁热治疗和自由基治疗，实现对乏氧肿瘤的高效安全治疗。本项目通过建立乳腺癌动物模型验证了此纳米体系在交变磁场的作用下显著地抑制肿瘤的增殖和复发。该研究克服了传统化疗毒副作用大和光治疗穿透深度浅的缺点，为交变磁场精准控制不依赖于氧的自由基释放应用于癌症治疗提供了新策略，同时也为研究自由基在肿瘤微环境作用机制奠定了坚实的实验基础，并有望进一步拓宽磁性介孔纳米材料在生物医学领域中的应用。