Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Organic-Inorganic Composites, Bionanomaterials & Translational Engineering Laboratory, Beijing Key Laboratory of Bioprocess, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.
Key Laboratory of Antibiotic Bioengineering, Ministry of Health, Laboratory of Oncology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
Small. 2023 Mar;19(12):e2206503. doi: 10.1002/smll.202206503. Epub 2023 Jan 1.
Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnO -loaded polydopamine (MnO /PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnO /PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnO /PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnO /PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.
癌症干细胞 (CSCs) 是一种具有自我更新、无限增殖和对常见物理化学因素不敏感的细胞，是癌症转移、复发和化疗耐药的关键。现有的 CSCs 抑制策略主要基于小分子药物，但受到其脱靶毒性的限制。CSCs 和非 CSCs 之间的转换联系难以切断。在这项工作中，报道了一种基于负载 MnO 的聚多巴胺 (MnO/PDA) 纳米炸弹的纳米治疗策略，该纳米炸弹具有化学动力学、光动力、光热和生物降解特性，可同时抑制 CSCs 和非 CSCs。MnO/PDA 纳米炸弹可以通过产生热疗、氧化应激和缓解缺氧直接破坏 CSCs 的微环境和致瘤能力。随后下调 CSCs 的标志物，导致 CSCs 的清除。同时，MnO/PDA 纳米炸弹介导的协同治疗可以直接消融大量肿瘤细胞，从而阻断 CSCs 转化的供应。为了肿瘤靶向，MnO/PDA 被巨噬细胞膜包裹。在结直肠癌 (CRC) 模型中，协同治疗的最终肿瘤抑制率为 70.8%。总之，这项工作可能为探索基于纳米材料的协同治疗方法来同时消除治疗耐药性 CSCs 和非 CSCs 开辟了新途径。
