Yang Yilin, Wang Ning, Wang Zhihua, Yan Fei, Shi Zhan, Feng Shouhua
State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, China.
ACS Nano. 2025 Jan 14;19(1):885-899. doi: 10.1021/acsnano.4c12304. Epub 2025 Jan 3.
Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal-organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnO/(A/R)TiO (MTO) in situ from MIL-125-NH (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation. Upon reaching the tumor sites, MTO effectively depleted glutathione to alleviate the suppressive tumor environment, and the heterojunctions and MnO in MTO facilitated SDT and synergistic chemodynamic therapy (CDT), respectively, leading to enhanced immunogenic cell death (ICD). Furthermore, Mn uptake by dendritic cells (DCs) and the tumor-associated antigens released due to ICD activated the stimulator of interferon genes pathway, which elicited a robust tumor-specific immune response by driving the maturation of DCs and the activation of T cells. In addition, the activated T cells secreted high levels of interferon-γ to enhance Mn/Mn-mediated ferroptosis in metastatic tumor cells. The combination of MTO-mediated synergistic therapy and PD-L1 checkpoint blockade exhibited vaccine-like functions, inducing stronger systemic immunity and durable immune memory to inhibit tumor progression, metastasis, and recurrence. To summarize, we synthesized a self-enhancing nanoplatform for synergistic SDT/CDT/immunotherapy using multifunctional MOF-derived Z-scheme heterojunctions. This study provides an experimental basis for amplifying the potential of sonosensitizers while optimizing SDT-mediated systemic immunity while avoiding interference caused by additional adjuvants.
尽管声动力疗法（SDT）在治疗恶性肿瘤方面具有潜力，但缺乏有效的声敏剂限制了其临床应用。在本研究中，我们通过调节锰源的添加量，探索了金属有机框架中杂原子掺杂浓度与热解后界面形成之间的关系，并成功地从MIL-125-NH₂（Ti/Mn）原位衍生出Z型异质结MnO/(A/R)TiO₂（MTO）。界面接触引入的电子转移途径促进了载流子分离，并极大地保留了有效的氧化还原成分，显著影响了活性氧生成的性能。到达肿瘤部位后，MTO有效地消耗了谷胱甘肽以缓解抑制性肿瘤环境，并且MTO中的异质结和MnO分别促进了SDT和协同化学动力疗法（CDT），导致免疫原性细胞死亡（ICD）增强。此外，树突状细胞（DCs）摄取的锰以及由于ICD释放的肿瘤相关抗原则激活了干扰素基因途径的刺激物，通过驱动DCs的成熟和T细胞的激活引发了强大的肿瘤特异性免疫反应。此外，活化的T细胞分泌高水平的干扰素-γ以增强Mn²⁺/Mn³⁺介导的转移性肿瘤细胞中的铁死亡。MTO介导的协同疗法与PD-L1检查点阻断的联合表现出疫苗样功能，诱导更强的全身免疫和持久的免疫记忆，以抑制肿瘤进展、转移和复发。总之，我们使用多功能金属有机框架衍生的Z型异质结合成了一种用于协同SDT/CDT/免疫治疗的自增强纳米平台。本研究为放大声敏剂的潜力提供了实验依据，同时优化了SDT介导的全身免疫，同时避免了额外佐剂引起的干扰。
