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Bacteria are the causative agents of various infectious diseases; however, the anti‐tumor effect of some bacterial species has attracted the attention of many scientists. The human oral cavity is inhabited by abundant and diverse bacterial communities and some of these bacterial communities could play a role in tumor suppression. Therefore, it is crucial to find oral bacterial species that show anti‐tumor activity on oral cancers. In the present study, we found that a high abundance of Porphyromonas gingivalis, an anaerobic periodontal pathogen, in the tumor microenvironment (TME) was positively associated with the longer survival of patients with oral squamous cell carcinoma (OSCC). An in vitro assay confirmed that P. gingivalis accelerated the death of OSCC cells by inducing cell cycle arrest at the G2/M phase, thus exerting its anti‐tumor effect. We also found that P. gingivalis significantly decreased tumor growth in a 4‐nitroquinoline‐1‐oxide‐induced in situ OSCC mouse model. The transcriptomics data demonstrated that P. gingivalis suppressed the biosynthesis of mucin O‐glycan and other O‐glycans, as well as the expression of chemokines. Validation experiments further confirmed the downregulation of mucin‐1 (MUC1) and C‐X‐C motif chemokine 17 (CXCL17) expression by P. gingivalis treatment. Flow cytometry analysis showed that P. gingivalis successfully reversed the immunosuppressive TME, thereby suppressing OSCC growth. In summary, the findings of the present study indicated that the rational use of P. gingivalis could serve as a promising therapeutic strategy for OSCC.

Abstract Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

ABSTRACT Oral disease, as a class of diseases with very high morbidity, brings great physical and mental damage to people worldwide. The increasing burden and strain on individuals and society make oral diseases an urgent global health problem. Since the treatment of almost all oral diseases relies on materials, the rapid development of advanced materials and technologies has also promoted innovations in the treatment methods and strategies of oral diseases. In this review, we systematically summarized the application strategies in advanced materials and technologies for oral diseases according to the etiology of the diseases and the comparison of new and old materials. Finally, the challenges and directions of future development for advanced materials and technologies in the treatment of oral diseases were refined. This review will guide the fundamental research and clinical translation of oral diseases for practitioners of oral medicine.

Cancer remains a significant global challenge, with an estimated 47% increase in cancer patients from 2020 to 2040. Increasing research has identified microorganism as a risk factor for cancer development. The oral cavity, second only to the colon, harbors more than 700 bacterial species and serves as a crucial microbial habitat. Although numerous epidemiological studies have reported associations between oral microorganisms and major systemic tumors, the relationship between oral microorganisms and cancers remains largely unclear. Current research primarily focuses on respiratory and digestive system tumors due to their anatomical proximity to the oral cavity. The relevant mechanism research mainly involves 47% dominant oral microbial population that can be cultured in vitro. However, further exploration is necessary to elucidate the mechanisms underlying the association between oral microbiota and tumors. This review systematically summarizes the reported correlations between oral microbiota and common cancers while also outlining potential mechanisms that may guide biological tumor treatment.

As a typical hallmark of solid tumors, hypoxia affects the effects of tumor radiotherapy, chemotherapy, and photodynamic therapy. Therefore, targeting the hypoxic tumor microenvironment (TME) is a promising treatment strategy for cancer therapy. Here, we prepared an Albumin Human Serum (HSA)-coated perfluorocarbon (PFC) carrying oxygen (PFC@O2) to minimize OSCC hypoxia. The results showed that PFC@O2 significantly downregulated the expression of HIF-1α and the number of M2-like macrophages in vitro. Furthermore, PFC@O2 effectively inhibited the growth of oral squamous cell carcinoma (OSCC) and reduced the proportion of negative immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and M2-like macrophages of TME in a 4-nitroquinoline N-oxide (4NQO)-induced mouse model. Conversely, the infiltration of CD4+ and CD8+ T cells was significantly increased in TME, suggesting that the anti-tumor immune response was enhanced. However, we also found that hypoxia-relative genes expression was positively correlated with CD68+/CD163+ TAMs in human tissue specimens. In summary, PFC@O2 could effectively inhibit the progression of OSCC by alleviating hypoxia, which provides a practical basis for gas therapy and gas synergistic therapy for OSCC.