School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China.
Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
Small. 2023 Dec;19(52):e2304014. doi: 10.1002/smll.202304014. Epub 2023 Aug 31.
Bacterial therapy is an emerging hotspot in tumor immunotherapy, which can initiate antitumor immune activation through multiple mechanisms. Porphyromonas gingivalis (Pg), a pathogenic bacterium inhabiting the oral cavity, contains a great deal of pathogen associated molecular patterns that can activate various innate immune cells to promote antitumor immunity. Owing to the presence of protoporphyrin IX (PpIX), Pg is also an excellent photosensitizer for photodynamic therapy (PDT) via the in situ generation of reactive oxygen species. This study reports a bacterial nanomedicine (nmPg) fabricated from Pg through lysozyme degradation, ammonium chloride lysis, and nanoextrusion, which has potent PDT and immune activation performances for oral squamous cell carcinoma (OSCC) treatment. To further promote the tumoricidal efficacy, a commonly used chemotherapeutic drug doxorubicin (DOX) is efficiently encapsulated into nmPg through a simple incubation method. nmPg/DOX thus prepared exhibits significant synergistic effects on inhibiting the growth and metastasis of OSCC both in vitro and in vivo via photodynamic-immunotherapy and chemotherapy. In summary, this work develops a promising bacterial nanomedicine for enhanced treatment of OSCC.
细菌疗法是肿瘤免疫治疗的一个新兴热点，它可以通过多种机制引发抗肿瘤免疫激活。牙龈卟啉单胞菌（Pg）是一种栖息在口腔中的致病菌，含有大量的病原体相关分子模式，可以激活各种固有免疫细胞，促进抗肿瘤免疫。由于存在原卟啉 IX（PpIX），Pg 也是一种极好的光动力疗法（PDT）光敏剂，可通过原位产生活性氧。本研究报告了一种通过溶菌酶降解、氯化铵裂解和纳米挤压从 Pg 制备的细菌纳米药物（nmPg），该药物具有强大的 PDT 和免疫激活性能，可用于治疗口腔鳞状细胞癌（OSCC）。为了进一步提高杀瘤效果，通过简单的孵育方法将一种常用的化疗药物阿霉素（DOX）高效包封入 nmPg 中。nmPg/DOX 因此制备出的药物在体外和体内通过光动力免疫治疗和化学治疗对抑制 OSCC 的生长和转移具有显著的协同作用。总之，这项工作开发了一种有前途的细菌纳米药物，用于增强口腔鳞状细胞癌的治疗效果。
