将靶向治疗和免疫疗法相结合为一体为癌症的完全治愈带来了希望。由于其选择性寄生和免疫激活能力，一些细菌有潜力实现靶向免疫疗法。在此，通过在厌氧痤疮丙酸杆菌（PA）（PA@LDH）上包覆NO3--插层的钴铝层状双氢氧化物（LDH），设计和合成了一种生物杂交系统。在该系统中，LDH的覆盖物减轻了PA对正常组织的致病性，并改变了其表面电荷以延长体内循环时间。一旦到达肿瘤部位，LDH的酸响应性降解使PA暴露。PA可以通过反硝化作用寄生并将硝酸盐转化为一氧化氮（NO）。然后，NO与细胞内的O2·-反应产生有毒的反应性氮种子ONOO-并引发肿瘤细胞凋亡。此外，从LDH释放的钴离子可以抑制超氧化物歧化酶（SOD）的活性，从而增加O2·-的水平并进一步增强抗肿瘤效果。此外，PA的寄生活性激活M2向M1巨噬细胞极化并引发一系列免疫反应，从而实现持续的抗肿瘤活性。体外和体内结果显示，该生物杂交系统能有效消除实体肿瘤并抑制肿瘤转移。总体而言，该生物杂交策略为实现免疫疗法和靶向治疗的同时提供了新的途径。

Combining targeted therapy and immunotherapy brings hope for a complete cancer cure. Due to their selective colonization and immune activation capacity, some bacteria have the potential to realize targeted immunotherapy. Herein, a biohybrid system was designed and synthesized by cladding NO3--intercalated cobalt aluminum layered double hydroxides (LDH) on anaerobic Propionibacterium acnes (PA) (PA@LDH). In this system, the covering of LDH reduces the pathogenicity of PA to normal tissues and alters its surface charge for prolonged in vivo circulation. Once the tumor site is reached, the acid-responsive degradation of LDH enables PA exposure. PA can colonize and convert nitrate ions to nitric oxide (NO) through denitrification. Then, NO reacts with intracellular O2·- to produce toxic reactive nitrogen species ONOO- and induce tumor cell apoptosis. In addition, cobalt ions released from LDH can inhibit the activity of superoxide dismutase (SOD), thus increasing the level of O2·- and further enhancing the antitumor effect. Moreover, PA exposure activates M2-to-M1 macrophage polarization and a range of immune responses, thereby achieving a sustained antitumor activity. In vitro and in vivo results reveal that the biohybrid system eliminates solid tumors and inhibits tumor metastasis effectively. Overall, the biohybrid strategy provides a new avenue for realizing simultaneous immunotherapy and targeted therapy.