Wrapping Porphyromonas gingivalis for tumor microenvironment immunomodulation and photothermal immunotherapy

Abstract Tumorigenic M2 phenotype macrophages, which are polarized by stimulating factors in the tumor microenvironment (TME), could facilitate tumor growth. They take participants in limiting T cells functions, tumor angiogenesis, tumor invasion, and metastasis. Increasing the ratio of M1 over M2 macrophages in TME is a promising strategy for cancer immunotherapy. Porphyromonas gingivalis (Pg) from the oral cavity could secrete melanin steadily, recruit macrophages and accelerate the conversion of macrophages to M1 phenotype. Here, we report a wrapping Porphyromonas gingivalis coated with the red blood cell membrane (cm) to generate cmPg to tune the ratio of M1 over M2 macrophages for cancer immunotherapy. The cm coating improves bacteria's size distribution, reduces their uptake by macrophages, and sustains the polarization behavior. In addition, the melanin in cmPg serves as photothermal therapy (PTT) agent under laser irradiation, enables cmPg to convert light to heat, and facilitates photothermal-induced immunogenic cell death (ICD) of cancer cells. Our bioinspired immunomodulatory bacteria can inhibit the growth of the primary and secondary tumor in B16F10 melanoma and CT26 colon cancer with the help of laser and anti-PD-1. Our work offers a straightforward strategy to upcycle Pg as biocompatible materials for combined photothermal immunotherapy.