She Yaoguang, Cui Jianxin, Ye Jiamin, Pan Fei, Liang Wenquan, He Xiaofeng, Wu Di, Ji Xiaoyuan, Wang Chunxi
Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China; Medical School of Chinese PLA, Beijing, 100853, China.
Department of General Surgery, First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.
Biomaterials. 2025 Nov;322:123354. doi: 10.1016/j.biomaterials.2025.123354. Epub 2025 Apr 20.
Peritoneal metastasis (PM) is a terminal stage of gastrointestinal cancers, often resulting in poor survival outcomes. Traditional treatments like cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown some effectiveness but are associated with significant risks. This study presents a novel nanomotor-based drug delivery system (M@MnO-Au-mSiO@CDDP) designed to enhance the efficacy of PM treatment. By utilizing an oxygen-driven heterojunction nanomotor (MnO-Au-mSiO), coated with membrane of M1-type macrophages, the system targets PM tumors with high precision through intraperitoneal perfusion. These biomimetic NMs promote deep tumor penetration, enhance reactive oxygen species (ROS) generation, and activate the STING pathway, a critical component in immune regulation. The catalytic properties of MnO within the nanomotors enhance drug permeability and retention, enabling targeted and controlled drug release. Both in vitro and in vivo experiments demonstrated the system's ability to significantly inhibit tumor growth, induce apoptosis, and activate immune responses. In addition, the synergistic effect of targeted drug delivery, catalytic therapy and immunotherapy of this system was further confirmed by constructing an in vitro gastric cancer organoid model, showing great clinical application potential. The study also confirmed excellent biocompatibility and stability, making these NMs a promising clinical tool for the treatment of PM. This research underscores the potential of nanotechnology to revolutionize cancer treatment by overcoming the limitations of traditional therapies and paving the way for future innovations in targeted cancer therapies.
腹膜转移（PM）是胃肠道癌症的终末期，常常导致不良的生存结局。像细胞减灭术（CRS）和热灌注化疗（HIPEC）等传统治疗方法已显示出一定疗效，但也伴随着重大风险。本研究提出了一种基于新型纳米马达的药物递送系统（M@MnO-Au-mSiO@CDDP），旨在提高PM治疗的疗效。该系统利用涂有M1型巨噬细胞膜的氧驱动异质结纳米马达（MnO-Au-mSiO），通过腹腔灌注高精度地靶向PM肿瘤。这些仿生纳米马达促进肿瘤深部渗透，增强活性氧（ROS）生成，并激活免疫调节中的关键成分——STING通路。纳米马达内MnO的催化特性增强了药物的渗透性和滞留性，实现靶向和可控的药物释放。体外和体内实验均证明该系统具有显著抑制肿瘤生长、诱导细胞凋亡和激活免疫反应的能力。此外，通过构建体外胃癌类器官模型进一步证实了该系统靶向给药、催化治疗和免疫治疗的协同效应，显示出巨大的临床应用潜力。该研究还证实了其优异的生物相容性和稳定性，使这些纳米马达成为治疗PM的一种有前景的临床工具。这项研究强调了纳米技术通过克服传统疗法的局限性，为未来靶向癌症治疗的创新铺平道路，从而彻底改变癌症治疗的潜力。
