工程化益生菌将光热铜死亡与生物力学破坏及免疫激活相结合
Engineered probiotics couple photothermal cuproptosis with biomechanical disruption and immune activation.
摘要(中文译文)
活细菌疗法面临表面功能化不佳和肿瘤微环境恶劣的限制。在此，我们通过对Nissle 1917进行聚多巴胺包覆，构建了EPACS（EcN@PDA/Au-CuS），聚多巴胺作为黏附性界面平台，引导Au-CuS异质结在细菌表面均匀生长。EPACS集肿瘤定植、高光热转换和刺激响应性铜释放于一体，用于铜死亡介导的联合光热治疗。在机制上，EPACS诱导氧化应激和线粒体功能障碍，触发铜死亡和细胞凋亡，同时原子力显微镜（AFM）揭示了动态生物力学变化——初期RhoA/F-actin依赖的细胞硬化，随后经激光照射逆转为不可逆的细胞骨架破坏和增强的细胞杀伤。EPACS实现了有效的肿瘤蓄积和光热加热，导致显著的肿瘤抑制且具有良好的生物安全性。当与激光照射联合时，EPACS减少胶原沉积和α-SMA表达，表明基质重塑，AFM证实了光热对肿瘤基质力学的破坏。这种生物力学重塑伴随免疫调节——M2样巨噬细胞和调节性T细胞减少——提示抗肿瘤免疫增强。总体而言，EPACS整合了生化损伤、铜死亡/细胞凋亡、生物力学调控和免疫调节，提供了一种有前景的联合癌症治疗策略。
Abstract
Living bacterial therapeutics face limitations from poor surface functionalization and a hostile tumor microenvironment. Here, we engineer EPACS (EcN@PDA/Au-CuS) by coating Nissle 1917 with polydopamine, which acts as an adhesive interfacial platform to direct the uniform growth of Au-CuS heterojunctions across the bacterial surface. EPACS combines tumor colonization, high photothermal conversion, and stimuli-responsive Cu release for combined cuproptosis-mediated photothermal therapy. Mechanistically, EPACS induces oxidative stress and mitochondrial dysfunction, triggering both cuproptosis and apoptosis, while atomic force microscopy (AFM) reveals dynamic biomechanical changes-an initial RhoA/F-actin-dependent cellular stiffening that is subsequently reversed by laser irradiation into irreversible cytoskeletal disruption and enhanced cell killing. , EPACS achieves effective tumor accumulation and photothermal heating, resulting in substantial tumor suppression with favorable biosafety. When combined with laser irradiation, EPACS reduces collagen deposition and α-SMA expression, indicating stromal remodeling, and AFM confirms photothermal disruption of tumor matrix mechanics. This biomechanical remodeling is accompanied by immune modulation-decreased M2-like macrophages and regulatory T cells-suggesting enhanced antitumor immunity. Overall, EPACS integrates biochemical damage, cuproptosis/apoptosis, biomechanical regulation, and immunomodulation, offering a promising combined cancer therapy.
如何引用
AMA
Xiaoyang Zhang, Xiaohui Liu, Ke Huang, Baijiang Jin, Nan Ma, Hao Liu, et al. Engineered probiotics couple photothermal cuproptosis with biomechanical disruption and immune activation.. Bioactive materials. 2027; doi:10.1016/j.bioactmat.2026.09.021.
APA
Xiaoyang Zhang, Xiaohui Liu, Ke Huang, Baijiang Jin, Nan Ma, Hao Liu, et al (2027). Engineered probiotics couple photothermal cuproptosis with biomechanical disruption and immune activation.. Bioactive materials. https://doi.org/10.1016/j.bioactmat.2026.09.021
GB/T 7714
Xiaoyang Zhang, Xiaohui Liu, Ke Huang, Baijiang Jin, Nan Ma, Hao Liu, et al. Engineered probiotics couple photothermal cuproptosis with biomechanical disruption and immune activation.[J]. Bioactive materials, 2027 doi:10.1016/j.bioactmat.2026.09.021.
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