NIR-IIb-triggered microbial upconversion photosynthesis enables hypoxia-resistant tumor lactate catabolism

IF 9.4 2区 材料科学 Q1 CHEMISTRY, PHYSICAL
Bingzhu Zheng, Feiyu Li, Jiafei Chen, Qilong Yan, Renren Deng, Li Zhi, Jian Ruan, Xiang Li
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引用次数: 0

Abstract

Elevated lactate levels in solid tumors contribute to immunosuppression, metabolic reprogramming, and resistance to therapy. Although lactate oxidase (LOX) offers a viable strategy for in situ lactate depletion, its therapeutic efficacy is fundamentally limited by tumor hypoxia due to the oxygen dependence of LOX. Here, we report a hybrid nanomaterial-microbial system that enables hypoxia-resistant lactate catabolism through NIR-Ⅱb-triggered upconverson photosynthesis. This system integrates LOX-producing Escherichia coli (E. coli) with Chlorella (Chl) and lanthanide-doped upconversion nanoparticles (UCNPs), which convert deeply penetrating 1550 nm light into visible emission to drive oxygenic photosynthesis. Unlike conventional photosynthetic oxygenation approaches limited by shallow visible light penetration, this system enables spatiotemporally controlled oxygen generation deep within tumors, sustaining LOX activity under hypoxia. In murine tumor models, the hybrid symbionts significantly inhibited tumor growth, promoted T cell infiltration, and induced durable immune memory. This work establishes a versatile optogenetic-metabolic platform for overcoming oxygen-limited metabolism in cancer therapy via deep-tissue-activatable microbial photosynthesis.
nir - iib触发的微生物上转化光合作用使耐缺氧的肿瘤乳酸分解代谢
实体瘤中乳酸水平升高有助于免疫抑制、代谢重编程和对治疗的抵抗。尽管乳酸氧化酶(LOX)为原位乳酸消耗提供了可行的策略,但由于LOX的氧依赖性,其治疗效果从根本上受到肿瘤缺氧的限制。在这里,我们报道了一种混合纳米材料-微生物系统,该系统通过NIR-Ⅱb触发的上转换光合作用实现耐缺氧乳酸分解代谢。该系统将产lox的大肠杆菌(E. coli)、小球藻(Chl)和镧系掺杂的上转换纳米粒子(UCNPs)结合在一起,将穿透1550 nm的深光转化为可见光,以驱动氧光合作用。与传统的受浅层可见光穿透限制的光合氧化方法不同,该系统能够在肿瘤深处实现时空控制的氧气生成,在缺氧条件下维持LOX活性。在小鼠肿瘤模型中,杂交共生体显著抑制肿瘤生长,促进T细胞浸润,诱导持久免疫记忆。这项工作建立了一个多用途的光遗传代谢平台,通过深层组织可激活的微生物光合作用克服癌症治疗中的氧限制代谢。
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来源期刊
Nano Research
Nano Research 化学-材料科学:综合
CiteScore
14.30
自引率
11.10%
发文量
2574
审稿时长
1.7 months
期刊介绍: Nano Research is a peer-reviewed, international and interdisciplinary research journal that focuses on all aspects of nanoscience and nanotechnology. It solicits submissions in various topical areas, from basic aspects of nanoscale materials to practical applications. The journal publishes articles on synthesis, characterization, and manipulation of nanomaterials; nanoscale physics, electrical transport, and quantum physics; scanning probe microscopy and spectroscopy; nanofluidics; nanosensors; nanoelectronics and molecular electronics; nano-optics, nano-optoelectronics, and nano-photonics; nanomagnetics; nanobiotechnology and nanomedicine; and nanoscale modeling and simulations. Nano Research offers readers a combination of authoritative and comprehensive Reviews, original cutting-edge research in Communication and Full Paper formats. The journal also prioritizes rapid review to ensure prompt publication.
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