清除氧自由基可杀死三阴性乳腺癌细胞

　　肿瘤微环境的氧自由基浓度增加，可严重抑制免疫应答引起的肿瘤细胞死亡以及肿瘤浸润淋巴细胞对肿瘤的杀伤作用。因此，调节细胞外氧自由基浓度，对于逆转免疫抑制环境至关重要。

　　2020年10月2日，英国《自然》旗下《自然通讯》在线发表中国福州大学化学学院、美国国家卫生研究院（NIH）国家生物医学成像和生物工程研究所（NIBIB）的研究报告，探讨了精准清除三阴性乳腺癌细胞外氧自由基的靶向方法。

　　该研究开发了一种针对肿瘤细胞外基质氧自由基的纳米清除剂，外层包裹着对酸碱度敏感的共价交联聚乙二醇。由于肿瘤细胞外基质为酸性，该共价交联聚乙二醇可吸附至肿瘤细胞外基质，并释放纳米清除剂，从而清除肿瘤微环境的氧自由基，恢复免疫应答引起的肿瘤细胞死亡，并延长肿瘤浸润淋巴细胞的存活时间，有助于个体化癌症免疫治疗。

　　该研究利用三阴性乳腺癌细胞（4T1）建立小鼠乳腺癌模型，证实该纳米清除剂清除肿瘤微环境的氧自由基可诱发抗肿瘤免疫力，并增加肿瘤浸润淋巴细胞，从而产生强大的抗肿瘤作用。

　　因此，该研究结果表明，利用先进的纳米材料可靶向清除肿瘤细胞外氧自由基，有望成为增强三阴性乳腺癌免疫治疗效果的新策略，故有必要进一步开展临床研究进行验证。

Nat Commun. 2020 Oct 2;11(1):4951.

Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death.

Hongzhang Deng, Weijing Yang, Zijian Zhou, Rui Tian, Lisen Lin, Ying Ma, Jibin Song, Xiaoyuan Chen.

College of Chemistry, Fuzhou University, Fuzhou, China; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, MD, USA.

Immunogenic cell death (ICD) and tumour-infiltrating T lymphocytes are severely weakened by elevated reactive oxygen species (ROS) in the tumour microenvironment. It is therefore of critical importance to modulate the level of extracellular ROS for the reversal of immunosuppressive environment. Here, we present a tumour extracellular matrix (ECM) targeting ROS nanoscavenger masked by pH sensitive covalently crosslinked polyethylene glycol. The nanoscavenger anchors on the ECM to sweep away the ROS from tumour microenvironment to relieve the immunosuppressive ICD elicited by specific chemotherapy and prolong the survival of T cells for personalized cancer immunotherapy. In a breast cancer model, elimination of the ROS in tumour microenvironment elicited antitumour immunity and increased infiltration of T lymphocytes, resulting in highly potent antitumour effect. The study highlights a strategy to enhance the efficacy of cancer immunotherapy by scavenging extracellular ROS using advanced nanomaterials.

DOI: 10.1038/s41467-020-18745-6