Wang Jing, Yu Weiqiang, Shen Hui, Sang Yanxiang, Zhang Hongjie, Zheng Benyan, Peng Xue, Hu Yuan, Ma Xiaopeng, Yang Zhenye, Yu Fazhi
Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, P. R. China.
HIM-BGI Omics Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences (CAS), Hangzhou, P. R. China.
Adv Sci (Weinh). 2025 Apr;12(14):e2414779. doi: 10.1002/advs.202414779. Epub 2025 Jan 22.
Black phosphorus (BP) has demonstrated potential as a drug carrier and photothermal agent in cancer therapy; however, its intrinsic functions in cancer treatment remain underexplored. This study investigates the immunomodulatory effects of polyethylene glycol-functionalized BP (BP-PEG) nanosheets in breast cancer models. Using immunocompetent mouse models-including 4T1 orthotopic BALB/c mice and MMTV-PyMT transgenic mice, it is found that BP-PEG significantly inhibits tumor growth and metastasis without directly inducing cytotoxicity in tumor cells. Mass cytometry analysis reveals that BP-PEG reshapes the tumor immune microenvironment by recruiting neutrophils. Neutrophil depletion experiments further demonstrate that the antitumor effects of BP-PEG are dependent on neutrophils. Moreover, bulk and single-cell RNA sequencing indicate that BP-PEG is mainly taken up by macrophages, leading to the release of inflammatory factors such as IL1A and CXCL2, which enhance neutrophil recruitment and activation, thereby amplifying the antitumor immune response. Finally, co-culture assays confirm that BP-PEG indeed enhances the antitumor activity of neutrophils and natural killer (NK) cells. These findings position BP-PEG as an immunomodulatory agent capable of reprogramming the tumor microenvironment to promote innate immunity against breast cancer. By stimulating neutrophil-mediated antitumor activity, BP-PEG offers a unique therapeutic approach that can potentially enhance the efficacy of existing cancer immunotherapies.
黑磷（BP）已在癌症治疗中展现出作为药物载体和光热剂的潜力；然而，其在癌症治疗中的内在功能仍未得到充分探索。本研究调查了聚乙二醇功能化黑磷（BP-PEG）纳米片在乳腺癌模型中的免疫调节作用。使用具有免疫活性的小鼠模型——包括4T1原位BALB/c小鼠和MMTV-PyMT转基因小鼠，发现BP-PEG能显著抑制肿瘤生长和转移，而不会直接诱导肿瘤细胞的细胞毒性。质谱流式细胞术分析表明，BP-PEG通过招募中性粒细胞重塑肿瘤免疫微环境。中性粒细胞耗竭实验进一步证明，BP-PEG的抗肿瘤作用依赖于中性粒细胞。此外，批量和单细胞RNA测序表明，BP-PEG主要被巨噬细胞摄取，导致IL1A和CXCL2等炎症因子的释放，这些因子增强了中性粒细胞的招募和激活，从而放大了抗肿瘤免疫反应。最后，共培养试验证实，BP-PEG确实增强了中性粒细胞和自然杀伤（NK）细胞的抗肿瘤活性。这些发现将BP-PEG定位为一种免疫调节因子，能够重新编程肿瘤微环境以促进针对乳腺癌的先天免疫。通过刺激中性粒细胞介导的抗肿瘤活性，BP-PEG提供了一种独特的治疗方法，有可能提高现有癌症免疫疗法的疗效。
