Guangdong Provincial Key Laboratory of Urology, Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou Institute of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
School of Medicine, South China University of Technology, Guangzhou 510006, China.
ACS Nano. 2024 May 14;18(19):12261-12275. doi: 10.1021/acsnano.4c00844. Epub 2024 Apr 29.
Cancer immunotherapy holds significant promise for addressing diverse malignancies. Nevertheless, its efficacy remains constrained by the intricate tumor immunosuppressive microenvironment. Herein, a light-triggered nanozyme Fe-TCPP-R848-PEG (Fe-MOF-RP) was designed for remodeling the immunosuppressive microenvironment. The Fe-TCPP-MOFs were utilized not only as a core catalysis component against tumor destruction but also as a biocompatible delivery vector of an immunologic agonist, improving its long circulation and tumor enrichment. Concurrently, it catalyzes the decomposition of HO within the tumor, yielding oxygen to augment photodynamic therapy. The induced ferroptosis, in synergy with photodynamic therapy, prompts the liberation of tumor-associated antigens from tumor cells inducing immunogenic cell death. Phototriggered on-demand release of R848 agonists stimulated the maturation of dendritic cells and reverted the tumor-promoting M2 phenotypes into adoptive M1 macrophages, which further reshaped the tumor immunosuppressive microenvironment. Notably, the nanozyme effectively restrains well-established tumors, such as B16F10 melanoma. Moreover, it demonstrates a distal tumor-inhibiting effect upon in situ light treatment. What is more, in a lung metastasis model, it elicits robust immune memory, conferring enduring protection against tumor rechallenge. Our study presents a straightforward and broadly applicable strategy for crafting nanozymes with the potential to effectively thwart cancer recurrence and metastasis.
癌症免疫疗法在治疗多种恶性肿瘤方面具有重要的应用前景。然而,其疗效仍然受到复杂的肿瘤免疫抑制微环境的限制。在这里,设计了一种光触发的纳米酶 Fe-TCPP-R848-PEG(Fe-MOF-RP),用于重塑免疫抑制微环境。Fe-TCPP-MOF 不仅作为一种核心催化成分用于对抗肿瘤破坏,还作为一种免疫激动剂的生物相容性递送载体,提高了其长循环和肿瘤富集能力。同时,它可以在肿瘤内分解 HO,产生氧气以增强光动力治疗。诱导的铁死亡与光动力治疗协同作用,促使肿瘤相关抗原从肿瘤细胞中释放,诱导免疫原性细胞死亡。光触发按需释放 R848 激动剂刺激树突状细胞的成熟,并将肿瘤促进的 M2 表型逆转成适应性 M1 巨噬细胞,进一步重塑肿瘤免疫抑制微环境。值得注意的是,该纳米酶有效地抑制了已建立的肿瘤,如 B16F10 黑色素瘤。此外,它在原位光治疗时表现出对远处肿瘤的抑制作用。更重要的是,在肺转移模型中,它引发了强大的免疫记忆,对肿瘤再挑战提供持久的保护。我们的研究提出了一种简单而广泛适用的策略,用于制备具有有效阻止癌症复发和转移潜力的纳米酶。
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