纳米疫苗对于有效的抗原递送和肿瘤特异性免疫已经引起了强烈的兴趣。开发更有效和个性化的纳米疫苗以通过利用纳米颗粒的固有性质来最大化疫苗接种级联的所有步骤是具有挑战性的。这里,合成了由氧化锰纳米颗粒和阳离子聚合物组成的可生物降解的纳米杂化物(MP),以加载模型抗原卵清蛋白以形成MPO纳米疫苗。更有趣的是,MPO可以作为自体纳米疫苗用于个性化肿瘤治疗,利用由免疫原性细胞死亡(ICD)诱导的原位释放的肿瘤相关抗原。MP纳米杂化物的固有特性,包括形态,尺寸,表面电荷,化学,和免疫调节功能被充分利用以增强级联的所有步骤并诱导ICD。MP纳米杂化物旨在通过阳离子聚合物有效地封装抗原,通过适当的大小引流到淋巴结,通过粗糙形态被树突状细胞(DC)内化,通过cGAS-STING途径诱导DC成熟,并通过“质子海绵效应”增强溶酶体逃逸和抗原交叉呈递。发现MPO纳米疫苗在淋巴结中有效积累,并引起强烈的特异性T细胞免疫反应,以抑制表达卵清蛋白的B16-OVA黑色素瘤的发生。此外,MPO通过ICD诱导产生自体抗原储库,显示出作为个性化癌症疫苗的巨大潜力。激活有效的抗肿瘤免疫力,和逆转免疫抑制。这项工作通过利用纳米杂种的固有特性,为构建个性化纳米疫苗提供了一种简便的策略。
Nanovaccines have attracted intense interests for efficient antigen delivery and tumor-specific immunity. It is challenging to develop a more efficient and personalized nanovaccine to maximize all steps of the vaccination cascade by exploiting the intrinsic properties of nanoparticles. Here, biodegradable nanohybrids (MP) composed of manganese oxide nanoparticles and cationic polymers are synthesized to load a model antigen ovalbumin to form MPO nanovaccines. More interestingly, MPO could serve as autologous nanovaccines for personalized tumor treatment taking advantage of in situ released tumor-associated antigens induced by immunogenic cell death (ICD). The intrinsic properties of MP nanohybrids including morphology, size, surface charge, chemical, and immunoregulatory functions are fully exploited to enhance of all steps of the cascade and induce ICD. MP nanohybrids are designed to efficiently encapsulate antigens by cationic polymers, drain to lymph nodes by appropriate size, be internalized by dendritic cells (DCs) by rough morphology, induce DC maturation through cGAS-STING pathway, and enhance lysosomal escape and antigen cross-presentation through the \"proton sponge effect\". The MPO nanovaccines are found to efficiently accumulate in lymph nodes and elicit robust specific T-cell immune responses to inhibit the occurrence of ovalbumin-expressing B16-OVA melanoma. Furthermore, MPO demonstrate great potential to serve as personalized cancer vaccines through the generation of autologous antigen depot through ICD induction, activation of potent antitumor immunity, and reversal of immunosuppression. This work provides a facile strategy for the construction of personalized nanovaccines by exploiting the intrinsic properties of nanohybrids.