使用亚单位纳米疫苗接种是对抗病毒感染和肿瘤发展的有希望的策略。然而,目前纳米疫苗的免疫原性对于临床翻译仍不满意。这里,我们开发了一种装载STING激动剂的纳米疫苗,2\'3\'-cGAMP和,模型亚基抗原,OVA,通过使用明确定义的可自行降解的聚(β-氨基酯)来治疗B16F10-OVA黑色素瘤肿瘤。聚合物在pH5.5下经历缓慢水解,但在pH>6.5下由沿聚酯链的氨基诱导自降解。结果表明,自降解产物促进了2'3'-cGAMP和OVA从早期内溶体释放到细胞质中,其中两个成分强烈激活CD8+T淋巴细胞(CTLs)和显着增强Ifn1,TNF,Cxcl9和Cxcl10表达。反过来,肿瘤微环境从冷到热重塑。此外,瘤内注射后,纳米疫苗可以迅速引流到前哨淋巴结。具有强免疫原性的纳米疫苗还可以减少分子2\'3\'-cGAMP引起的全身性炎症反应的副作用。动物的肿瘤进展受到抑制,他们的存活率显著提高。因此,多功能生物可降解材料为癌症疫苗提供了一种新的递送系统,可转化为临床。
Vaccination with subunit nanovaccines is a promising strategy to combat virus infection and tumor development. However, immunogenicity of present nanovaccines is still unsatisfied for clinical translation. Here, we developed a nanovaccine loading a STING agonist, 2\'3\'-cGAMP and, a model subunit antigen, OVA, by using a well-defined self-degradable poly(β-amino ester)s to treat B16F10-OVA melanoma tumors. The polymer underwent slow hydrolysis at pH 5.5 but self-degraded induced by the amino groups along the polyester chain at pH > 6.5. It is shown that the self-degradation products facilitated the release of 2\'3\'-cGAMP and OVA from early endolysome to the cytosol, where the two components strongly activated CD8+ T lymphocytes (CTLs) and significantly enhanced Ifn1, TNF, Cxcl9, and Cxcl10 expression. In turn, the tumor microenvironment was remolded from cold to hot. Moreover, the nanovaccine could be quickly drained to sentinel lymph nodes after intratumoral injection. The nanovaccine with strong immunogenicity also could reduce the side effects of systemic inflammatory reaction caused by molecular 2\'3\'-cGAMP. The tumor progression of animals was inhibited, and their survival rates increased significantly. Thus, the multifunctional biodegradable material provided a new delivery system for a cancer vaccine to translate to clinics.