Emerging roles of exosomes in oral diseases progression

Abstract

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.

Fig. 1

Exosomes in OSCCs. Exosomes play crucial roles in several key processes through OSCCs progression. a Addition of exosomal miR-10b and increased level of several exosomal lncRNAs (targeting PI3K-AKT-mTOR pathway) lead to initiation of OSCCs. b OSCC cells derived exosomal miR-130b-3p and miR-23b-3p promoted angiogenesis through downregulating PTEN, while miR-221s and miR-210-3p activated through PI3K/AKT pathway. MSCs-derived MMP1 played the same role in angiogenesis. c During the progression of OSCCs, TME exhibits intricate interactions with tumors. Exosomes derived from OSCC cells promoted differentiation of CAFs, while CAFs secreted exosomal miR-382-5p and miR-146b-5p to enhance tumor development. In immune regulations, cancer-derived exosomal THBS-1 induced polarization of TAMs toward M1 type. Exosomal UCA1, miR-29a-3p, CMTM6, HSP-90 and PD-L1 (under ER stress) lead TAMs to M2 type. Both M1 and M2 macrophages contribute to the progression of malignancy. T cells were also modulated by cancer cells through exosomal circ_0069313, targeting PD-L1. In addition, Tregs played a crucial role in facilitating immune evasion in OSCCs. d Exosomes can regulate treatment response of OSCC to chemotherapy and radiotherapy

Fig. 2

Schematic illustration of exosomal detection techniques. a Differential centrifugation can isolate exosome cargos at different fractions. b Surface enhancement Raman spectroscopy (SERS) demonstrates distinct Raman spectra between saliva samples from HNSCC and healthy control groups. c Modified mass spectrometry with CD63 capturing allows for quantitative analysis of exosomes. c-1 Detection of exosomal signal is achieved through cholesterol-based rolling circle amplification and gold-nanoparticle-labeled DNA. c-2 Red blood cell membrane (RBCM)-modified electrode can produce electrochemical signals of exosomes with Au nanoparticles

Fig. 3

Research flow for exosomes in oral diseases. Exosomes can be obtained from human fluids, such as saliva collected from the oral cavity, providing non-invasive methods for disease detection (a). Subsequently, exosomes are isolated from diverse sources, separated and analyzed by novel techniques (e.g., modified centrifugation) (b, c). The distinct effects of exosomes are then examined through in vitro and/or in vivo experiments (d). These comprehensive research findings contribute to the development of a systematic understanding of exosomes, serving as a foundation for clinical applications (e). Finally, with a well-established experimental basis, exosomes meet practical clinical applications in oral medicine (f)