Yang Meng, Meng Yang, Li Junling, Bai Liya, Cheng Yuanyuan, Liu Yuanyuan, Cao Mingxin, Yang Xiaoying, Wang Yinsong, Liu Yang
Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
Adv Sci (Weinh). 2025 Aug;12(30):e2505310. doi: 10.1002/advs.202505310. Epub 2025 May 14.
Bacterial cancer therapy recently has been attracting more and more attention because of its multiple functions to fight cancer. Porphyromonas gingivalis (Pg), a Gram-negative pathogenic bacterium, acquires protoporphyrin IX (PpIX) and iron from heme and synthesizes abundant µ-oxo bisheme on its cell walls (CWs). For the first time, it is found that the CWs extracted from Pg has intrinsic peroxidase (POD)-mimicking and sonodynamic activities owing to the presence of µ-oxo bisheme. In this study, the CWs of Pg are nanofabricated to form the CW vesicles (CWV) containing a large amount of lipopolysaccharide (LPS) and further encapsulated doxorubicin (DOX) to prepare DOX-loaded CWV (DOX@CWV), hoping to eradicate cancer by combining sonodynamic therapy (SDT), chemotherapy, and bacterial immunotherapy. The results confirmed that DOX@CWV can catalyze the conversion of HO into O and consume the reduced glutathione (GSH), and thus greatly boost their own sonodynamic performance upon ultrasonic irradiation. Both in vitro and in vivo, DOX@CWV efficiently inhibited cancer growth by combining SDT and chemotherapy, and also exerted synergistic anticancer immune effects of bacterial immunotherapy and SDT. In summary, the findings not only contribute a promising bacterial therapeutic agent but also provide a combination strategy for clinical cancer treatment.
近年来，细菌癌症治疗因其多种抗癌功能而受到越来越多的关注。牙龈卟啉单胞菌（Pg）是一种革兰氏阴性病原菌，可从血红素中获取原卟啉IX（PpIX）和铁，并在其细胞壁（CWs）上合成大量的μ-氧代双血红素。首次发现，从Pg中提取的CWs由于存在μ-氧代双血红素而具有内在的过氧化物酶（POD）模拟活性和超声动力学活性。在本研究中，对Pg的CWs进行纳米加工，形成含有大量脂多糖（LPS）的CW囊泡（CWV），并进一步包裹阿霉素（DOX）以制备负载DOX的CWV（DOX@CWV），希望通过结合超声动力学疗法（SDT）、化疗和细菌免疫疗法来根除癌症。结果证实，DOX@CWV可以催化HO转化为O并消耗还原型谷胱甘肽（GSH），从而在超声照射下大大提高其自身的超声动力学性能。在体外和体内，DOX@CWV通过结合SDT和化疗有效地抑制了癌症生长，并且还发挥了细菌免疫疗法和SDT的协同抗癌免疫作用。总之，这些发现不仅提供了一种有前景的细菌治疗剂，还为临床癌症治疗提供了一种联合策略。
