外泌体在宫颈癌形成及其诊疗中的作用

宫颈癌作为女性第2大恶性肿瘤，仍然是全球范围内的公共卫生问题。外泌体是活细胞主动分泌的一种具有脂质双分子层结构的纳米级囊泡，能够携带蛋白质、脂质、DNA和RNA (包括mRNA、miRNA、lncRNA和circRNA)等多种具有生物学活性的物质。作为新型的细胞间通讯分子，外泌体不仅参与细胞间正常的信息传递和物质交换等生物学进程，而且在宫颈癌的发生发展过程中发挥重要作用，例如，可通过调节肿瘤微环境来参与HPV感染、促进肿瘤细胞增殖、促进血管形成、参与免疫逃逸以及参与肿瘤的侵袭和转移。外泌体广泛分布于各种生物体液中，可由不同病变程度的宫颈细胞分泌，在阴道灌洗液和血浆中大量富集，且由于其结构的稳定性，因此有望作为一种新型液体活检标志物用于宫颈癌的早期诊断。此外，外泌体具有免疫原性低、稳定性好和穿透性强等特点，可以克服生物利用度低等多种缺点，增强药物的靶向性和药物效应，并且能够降低非靶向的细胞毒性和免疫原性，因此有潜力作为新一代药物或药物载体用于肿瘤的靶向治疗。本文将针对目前国内外关于外泌体在宫颈癌发生发展过程中的作用以及诊断治疗应用领域的最新研究进展加以综述，为临床宫颈癌的诊断和治疗中一种新型的生物标志物的研究提供依据。

The Application of Exosomes in the Development and Diagnosis and Treatment of Cervical Cancer

Cervical cancer, as the second malignant female cancer, remains a major public health problem worldwide. Exosomes, nanometer-sized extracellular vesicles enveloped in a lipid bilayer membrane, are released by living cells and carry a variety of proteins, lipids, DNA, RNA(including mRNA, miRNA, lncRNA and circRNA) and other biologically active substances. As a novel intercellular communication molecule, exosomes are not only involved in biological processes such as signaling and substance exchange, but also play an important role in the process of the occurrence and development of cervical cancer such as regulating the tumor microenvironment to participate in HPV infection and the immune escape, promoting tumor cell proliferation and blood vessel formation, and regulating the invasion and metastasis of tumor. Exosomes with stability structure, are secreted by cervical cells of different lesion degrees, are ubiquitous in various biological fluids and can be enriched in cervicovaginal lavage sample fluid and plasma, thus it is expected to be a new type of liquid biopsy marker for the early diagnosis of cervical cancer. In addition, exosomes have the characteristics of low immunogenicity, good stability and strong penetration, which can overcome many shortcomings such as low bioavailability and enhance the targeting and drug effect of drugs while reducing non targeted cytotoxicity and immunogenicity, thus it has the potential to be a new generation of drugs or drug carriers for tumor targeted therapy. This article reviews the latest research on the role of exosomes in the development of cervical cancer and the relevant clinical applications, aiming to provide the basis for novel biomarker for the clinical diagnosis and treatment of cervical cancer.