Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies. Here, we present a proton-driven nanotransformer-based vaccine, comprising a polymer–peptide conjugate-based nanotransformer and loaded antigenic peptide. The nanotransformer-based vaccine induces a strong immune response without substantial systemic toxicity. In the acidic endosomal environment, the nanotransformer-based vaccine undergoes a dramatic morphological change from nanospheres (about 100 nanometres in diameter) into nanosheets (several micrometres in length or width), which mechanically disrupts the endosomal membrane and directly delivers the antigenic peptide into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. The nanotransformer-based vaccine effectively inhibits tumour growth in the B16F10-OVA and human papilloma virus-E6/E7 tumour models in mice. Moreover, combining the nanotransformer-based vaccine with anti-PD-L1 antibodies results in over 83 days of survival and in about half of the mice produces complete tumour regression in the B16F10 model. This proton-driven transformable nanovaccine offers a robust and safe strategy for cancer immunotherapy.

癌症疫苗对改善癌症治疗有很大的希望。然而，肿瘤抗原的内体捕获和低免疫原性通常限制了疫苗接种策略的效率。在这里，我们提出了一种质子驱动的基于纳米变压器的疫苗，包括基于聚合物-肽偶联物的纳米变压器和负载的抗原肽。基于纳米变压器的疫苗可诱导强烈的免疫反应，而不会产生实质性的全身毒性。在酸性内体环境中，基于纳米转换器的疫苗经历了从纳米球（直径约 100 纳米）到纳米片（长或宽几微米）的巨大形态变化，这会机械地破坏内体膜并将抗原肽直接递送到细胞质。重新组装的纳米片还通过激活特定的炎症通路来增强肿瘤免疫力。基于纳米变压器的疫苗可有效抑制小鼠 B16F10-OVA 和人乳头瘤病毒-E6/E7 肿瘤模型中的肿瘤生长。此外，将基于纳米变压器的疫苗与抗 PD-L1 抗体相结合，可实现超过 83 天的生存期，并且在 B16F10 模型中，大约一半的小鼠会产生完全的肿瘤消退。这种质子驱动的可转化纳米疫苗为癌症免疫治疗提供了一种强大而安全的策略。将基于纳米变压器的疫苗与抗 PD-L1 抗体相结合，可导致超过 83 天的存活期，并且在 B16F10 模型中，大约一半的小鼠会产生完全的肿瘤消退。这种质子驱动的可转化纳米疫苗为癌症免疫治疗提供了一种强大而安全的策略。将基于纳米变压器的疫苗与抗 PD-L1 抗体相结合，可导致超过 83 天的存活期，并且在 B16F10 模型中，大约一半的小鼠会产生完全的肿瘤消退。这种质子驱动的可转化纳米疫苗为癌症免疫治疗提供了一种强大而安全的策略。