In situ-generated vaccine-like pyroptosome for personalized cancer immunotherapy

IF 38 1区材料科学 Q1 CHEMISTRY, PHYSICAL

Nature Materials Pub Date : 2026-03-03 DOI:10.1038/s41563-026-02506-9

Binlong Chen, Fangjie Wan, Heming Xia, Xingquan Pan, Letong Wang, Yaoqi Wang, Yue Yan, Jianxiong Liu, Mingmei Tang, Ye Yang, Mengmeng Qin, Jiaona Ren, Bushu Zhou, Lijun Zhong, Wei Chen, Chuanhui Han, Mi Deng, Qiang Zhang, Yiguang Wang

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Abstract

The efficacy of in situ cancer vaccination has been hampered by a poor spatiotemporal orchestration of multiple key steps of the cancer-immunity cycle in most tumours and systemic toxicity related to therapeutic strategies. Here we report a systemic injectable and pyroptosis-enabled nanoadjuvant that evokes the secretion of a vaccine-like pyroptosome in the tumour area for robust antitumour immunity. This systemic injectable and pyroptosis-enabled nanoadjuvant induces vigorous immunogenic pyroptosis, triggering the efficient release of tumour antigen-rich pyroptosomes, damage-associated molecular patterns and proinflammatory cytokines. Photoactivatable release of a TLR7/8 agonist into the pyroptosome generates an in situ cancer vaccine platform that cooperatively activates the cancer-immunity cycle and avoids systemic toxicity. The vaccine boosts both innate and adaptive immune responses, facilitating the eradication of primary tumours and metastatic nodules, thereby providing long-lasting cancer prevention. Overall, the rational design of pyroptosis-inducing nanomedicines for boosting the cancer-immunity cycle reported here might aid in the development of more efficient personalized cancer immunotherapy approaches. An injectable pH-sensitive nanoadjuvant is shown to induce effective pyroptosis of tumours, which, combined with the in situ photoactivable release of TLR agonists, generates a strong vaccine-like response to eradicate the tumour.

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在现场产生疫苗样焦体个体化癌症免疫治疗

在大多数肿瘤中，癌症免疫周期的多个关键步骤的时空协调不佳，以及与治疗策略相关的全身毒性，阻碍了原位癌症疫苗接种的有效性。在这里，我们报道了一种全身可注射的、具有焦亡功能的纳米佐剂，它能在肿瘤区域唤起疫苗样焦亡体的分泌，从而产生强大的抗肿瘤免疫。这种全身性可注射和热亡激活的纳米佐剂诱导剧烈的免疫原性热亡，触发富含肿瘤抗原的热亡体、损伤相关的分子模式和促炎细胞因子的有效释放。TLR7/8激动剂在焦体中的光激活释放可产生原位癌症疫苗平台，该平台可协同激活癌症免疫周期并避免全身毒性。该疫苗可增强先天和适应性免疫反应，促进原发性肿瘤和转移性结节的根除，从而提供长期的癌症预防。总的来说，本文报道的促进癌症免疫周期的热诱导纳米药物的合理设计可能有助于开发更有效的个性化癌症免疫治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Materials 工程技术-材料科学：综合

CiteScore

62.20

自引率

0.70%

发文量

221

审稿时长

3.2 months

期刊介绍： Nature Materials is a monthly multi-disciplinary journal aimed at bringing together cutting-edge research across the entire spectrum of materials science and engineering. It covers all applied and fundamental aspects of the synthesis/processing, structure/composition, properties, and performance of materials. The journal recognizes that materials research has an increasing impact on classical disciplines such as physics, chemistry, and biology. Additionally, Nature Materials provides a forum for the development of a common identity among materials scientists and encourages interdisciplinary collaboration. It takes an integrated and balanced approach to all areas of materials research, fostering the exchange of ideas between scientists involved in different disciplines. Nature Materials is an invaluable resource for scientists in academia and industry who are active in discovering and developing materials and materials-related concepts. It offers engaging and informative papers of exceptional significance and quality, with the aim of influencing the development of society in the future.