Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6−3.2 μm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.

癌症疫苗可以促进肿瘤特异性免疫刺激，是最重要的免疫治疗策略之一，在癌症治疗/预防方面具有巨大潜力。在这里，我们制备了一系列由负载多柔比星和酪氨酸激酶抑制剂和透明质酸包被的树突状聚合物组成的纳米颗粒（称为 HDDT 纳米颗粒），发现 HDDT 纳米颗粒可以将各种癌细胞转化为微米大小的囊泡（1.6-3.2 μm；称为 HMV），细胞到 HMV 的转换效率约为 100%。我们在两个荷瘤小鼠模型中证实，纳米粒子可以抑制肿瘤生长，诱导强烈的免疫原性细胞死亡，并通过原位产生 HMV 将原发性肿瘤转化为抗原库，用作癌症免疫治疗的个性化疫苗。此外，HDDT治愈的小鼠表现出很强的免疫记忆效应，HDDT治疗可以实现对肿瘤再攻击的长期保护。总的来说，目前的工作为制备含肿瘤相关抗原的囊泡和开发个性化癌症疫苗提供了一般策略。