State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Biomedical Materials of Natural Macromolecules, Beijing Laboratory of Biomedical Materials, College of Materials Sciences and Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, China.
Adv Mater. 2022 Mar;34(9):e2108263. doi: 10.1002/adma.202108263. Epub 2022 Jan 20.
The protumoral and immunosuppressive tumor microenvironments greatly limit the antitumor immune responses of nanoparticles for cancer immunotherapy. Here, the intrinsic immunomodulatory effects of orchestrated nanoparticles and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, are explored. By optimizing both the composition and morphology, a facile strategy is proposed to construct yolk-shell nanohybrids (Fe O @C/MnO -PGEA, FCMP). The intrinsic immunomodulatory effects of FCMP are utilized to reprogram macrophages to M1 phenotype and induce the maturation of dendritic cells. In addition, the chemical, magnetic, and optical properties of FCMP contribute to amplified immunogenic cell death induced by multiaugmented chemodynamic therapy (CDT) and synergistic tumor treatment. Taking advantage of the unique yolk-shell structure, accurate T -T dual-mode magnetic resonance imaging can be realized and CDT can be maximized through sufficient exposure of both the Fe O core and MnO shell. Potent antitumor effects are found to substantially inhibit the growth of both primary and distant tumors. Furthermore, the strategy can be extended to the synthesis of other yolk-shell nanohybrids with tailored properties. This work establishes a novel strategy for the fabrication of multifunctional nanoplatforms with yolk-shell structure for effective cancer therapy with immunomodulation-enhanced antitumor immunity.
肿瘤前和免疫抑制的肿瘤微环境极大地限制了纳米粒子用于癌症免疫治疗的抗肿瘤免疫反应。在这里，研究了协调纳米粒子的固有免疫调节作用及其同时触发肿瘤抗原释放的能力，从而逆转免疫抑制，实现强大的抗肿瘤免疫和增强的癌症治疗。通过优化组成和形态，提出了一种简便的策略来构建蛋黄壳纳米杂化物（Fe O @C/MnO -PGEA，FCMP）。FCMP 的固有免疫调节作用被利用来重新编程巨噬细胞为 M1 表型，并诱导树突状细胞成熟。此外，FCMP 的化学、磁性和光学性质有助于增强多增强化学动力学治疗（CDT）和协同肿瘤治疗引起的免疫原性细胞死亡。利用独特的蛋黄壳结构，可以实现准确的 T -T 双模态磁共振成像，并通过充分暴露 Fe O 核和 MnO 壳来最大化 CDT。发现强大的抗肿瘤作用可显著抑制原发性和远处肿瘤的生长。此外，该策略可扩展到具有定制性质的其他蛋黄壳纳米杂化物的合成。这项工作为具有免疫调节增强抗肿瘤免疫的多功能蛋黄壳结构纳米平台的构建建立了一种新策略，可有效进行癌症治疗。
