清华大学喻国灿小组宣布他们的研究发现基于器官囊过滤的胰腺靶向脂质纳米颗粒。该项研究成果发表在2026年2月25日出版的《自然》上。

在这里，课题组确定了胰腺选择性递送的明确和普遍原则，并提出了胰腺靶向脂质纳米颗粒（AH-LNP）用于mRNA递送。AH-LNP在与蛋白质组装后表现出体积增大，促进了胶囊过滤器介导的胰腺选择性积累和受体介导的内吞作用，从而增强了胰腺靶向能力。得益于此，AH-LNP通过递送Cas9 mRNA和单导RNA （sgRNA）在胰腺中实现了精确、高效的基因组编辑，在自身免疫性胰腺疾病的治疗中显示出良好的潜力。

此外，在多种胰腺癌模型中，通过AH-LNP靶向递送编码治疗性细胞因子的mRNA，与癌症疫苗或嵌合抗原受体T细胞治疗联合使用时，显示出卓越的抗肿瘤效果。在包括非人灵长类动物在内的多种动物模型中验证了AH-LNP的安全性和胰腺mRNA传递，显示了临床翻译的巨大前景。他们的发现强调了这种胰腺靶向机制及其衍生的LNP平台的变革潜力，为开发针对各种胰腺疾病的精确治疗方法开辟了道路。

据了解，实现胰腺靶向递送标志着胰腺疾病治疗的突破，但精确递送仍然具有挑战性。

附：英文原文

Title: Pancreatic-targeted lipid nanoparticles based on organ capsule filtration

Author: Lei, Jiaqi, Yang, Kai, Cao, Wanyue, Qi, Shaolong, Du, Xianlong, Li, Hongjian, Wang, Yangfan, Gan, Jinqun, Feng, Yunxuan, Li, Yongcan, Zhang, Wenjie, Bai, Bing, Lin, Xin, Su, Xinhui, Zhang, Qi, Liang, Tingbo, Yu, Guocan

Issue&Volume: 2026-02-25

Abstract: Achieving pancreatic-targeted delivery marks a breakthrough in treating pancreatic diseases, yet precise delivery remains challenging1. Here we identify an explicit and universal principle for pancreatic-selective delivery and propose a pancreatic-targeted lipid nanoparticle (AH-LNP) for mRNA delivery. AH-LNP exhibits size enlargement after assembly with proteins, facilitating capsule-filter-mediated pancreas-selective accumulation and receptor-mediated endocytosis, thereby boosting the pancreatic-targeted ability. Benefiting from this, AH-LNP enables precise and efficient genome editing in the pancreas through the delivery of Cas9 mRNA and single guide RNA (sgRNA), exhibiting promising potential in the treatment of autoimmune pancreatic diseases. Furthermore, pancreatic-targeted delivery of mRNA encoding therapeutic cytokines through AH-LNP demonstrates superior antitumour efficacy when combined with a cancer vaccine or chimeric antigen receptor T cell therapy in multiple pancreatic cancer models. The safety and pancreatic mRNA delivery of AH-LNP were verified in multiple animal models, including non-human primates, demonstrating great promise for clinical translation. Our findings highlight the transformative potential of this pancreatic-targeted mechanism and the derived LNP platform, opening avenues for developing precision therapeutics against diverse pancreatic diseases.

DOI: 10.1038/s41586-026-10158-7

Source: https://www.nature.com/articles/s41586-026-10158-7