Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Nano Lett. 2020 Jun 10;20(6):4487-4496. doi: 10.1021/acs.nanolett.0c01287. Epub 2020 May 21.
Cancer immunotherapy as a novel cancer therapeutic strategy has shown enormous promise. However, the immunosuppressive tumor microenvironment (ITM) is a primary obstacle. Tumor-associated macrophages (TAMs) as a major component of immune cells in a tumor microenvironment are generally polarized to the M2 phenotype that not only accelerates tumor growth but also influences the infiltration of lymphocytes and leads to immunosuppression. Thus, rebuilding ITM by re-educating TAMs and increasing infiltration of lymphocytes is a promising strategy. Herein, gadofullerene (GF-Ala) nanoparticles are demonstrated to reprogram TAMs to M1-like and increase the infiltration of cytotoxic T lymphocytes (CTLs), achieving effective inhibition of tumor growth. Notably, the modulation of ITM by GF-Ala promotes the anticancer efficacy of anti-PD-L1 immune checkpoint inhibitor, achieving superior synergistic treatment. Additionally, GF-Ala nanoparticles can be mostly excreted from the body and cause no obvious toxicity. Together, this study provides an effective immunomodulation strategy using gadofullerene nanoparticles by rebuilding ITM and synergizing immune checkpoint blockade therapy.
癌症免疫疗法作为一种新型癌症治疗策略，具有巨大的应用潜力。然而，免疫抑制性肿瘤微环境（ITM）是一个主要的障碍。肿瘤相关巨噬细胞（TAMs）作为肿瘤微环境中免疫细胞的主要组成部分，通常极化到 M2 表型，这不仅加速了肿瘤的生长，而且影响了淋巴细胞的浸润，导致免疫抑制。因此，通过重新教育 TAMs 和增加淋巴细胞浸润来重建 ITM 是一种很有前途的策略。本研究中，证实了全氟丁基纳米颗粒（GF-Ala）可将 TAMs 重编程为 M1 样，并增加细胞毒性 T 淋巴细胞（CTLs）的浸润，从而有效抑制肿瘤生长。值得注意的是，通过 GF-Ala 调节 ITM 可促进抗 PD-L1 免疫检查点抑制剂的抗癌疗效，实现了优异的协同治疗效果。此外，GF-Ala 纳米颗粒大部分可以从体内排出，没有明显的毒性。综上所述，该研究通过重建 ITM 并协同免疫检查点阻断治疗，提供了一种使用全氟丁基纳米颗粒的有效的免疫调节策略。
