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光敏剂诱导的 HPV16 E7 纳米疫苗用于宫颈癌免疫治疗。

Photosensitizer-induced HPV16 E7 nanovaccines for cervical cancer immunotherapy.

机构信息

Department of Obstetrics and Gynecology, Women's Hospital School of Medicine Zhejiang University, Hangzhou, Zhejiang province, 310000, PR China.

Shanghai East Hospital of Tongji University, Shanghai, 200120, PR China.

出版信息

Biomaterials. 2022 Mar;282:121411. doi: 10.1016/j.biomaterials.2022.121411. Epub 2022 Feb 14.

Abstract

There is a lack of effective treatment methods for advanced cervical, and the therapeutic HPV vaccine is a promising option. The design of an efficient therapeutic vaccine is one of the main challenges. In the current study, we constructed a novel HPV nanovaccine that could effectively inhibit the progression of cervical cancer by combining nanotechnology and photodynamic therapy. This nanovaccine was constructed by linking bovine serum albumin (BSA) with the E7 antigen and then encapsulating the photosensitizer and adjuvant through disulfide bonds to form a highly biocompatible and stable structure. Due to its slow-release properties and targeted delivery to lymph nodes combined with infrared laser irradiation of photosensitizers to produce a photo-oxygen response, this vaccine could effectively induce the maturation of dendritic cells and stimulate T cell effects, thereby enhancing antitumor immunity. This prevention and treatment of tumors was experimentally demonstrated in a TC-1 cervical cancer model in C57BL/6 mice. This strategy can be applied to the design of therapeutic HPV vaccines in the future for clinical use.

摘要

目前针对晚期宫颈癌缺乏有效的治疗方法,而治疗性 HPV 疫苗是一种很有前途的选择。设计有效的治疗性疫苗是主要挑战之一。在本研究中,我们构建了一种新型 HPV 纳米疫苗,通过结合纳米技术和光动力疗法,可有效抑制宫颈癌的进展。该纳米疫苗通过将牛血清白蛋白(BSA)与 E7 抗原连接,然后通过二硫键将光敏剂和佐剂包封,形成高度生物相容性和稳定的结构。由于其具有缓慢释放特性和靶向淋巴结的能力,结合光敏剂的红外激光照射产生光氧反应,该疫苗可有效诱导树突状细胞成熟并刺激 T 细胞效应,从而增强抗肿瘤免疫。在 C57BL/6 小鼠的 TC-1 宫颈癌模型中实验证明了这种肿瘤的预防和治疗效果。该策略可应用于未来治疗性 HPV 疫苗的设计,用于临床应用。

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