Therapeutic delivery selectively to lymph nodes has the potential to address a variety of unmet clinical needs. However, owing to the unique structure of the lymphatics and the size-restrictive nature of the lymph node reticular network, delivering cargo to specific cells in the lymph node cortex and paracortex is difficult. Here, we describe a delivery system to overcome lymphatic and intra-lymph node transport barriers by combining nanoparticles that are rapidly conveyed to draining lymph nodes after administration in peripheral tissues with programmable degradable linkers. This platform enables the controlled release of intra-lymph-mobile small-molecular cargo, which can reach vastly more immune cells throughout the lymph node than either the particles or free compounds alone. The release rate can be programmed, allowing access to different lymph node structures and therefore specific lymphocyte subpopulations. We are thus able to alter the subtypes of drugged lymph node cells to improve immunotherapeutic effects.

选择性地向淋巴结进行治疗递送有可能解决各种未满足的临床需求。然而，由于淋巴管的独特结构和淋巴结网状网络的大小限制性质，将货物运送到淋巴结皮质和副皮质中的特定细胞是困难的。在这里，我们描述了一种传递系统，通过将在外周组织中给药后迅速输送到引流淋巴结的纳米颗粒与可编程的可降解接头相结合，从而克服淋巴和淋巴结内运输障碍。该平台能够控制释放淋巴内移动的小分子货物，与单独的颗粒或游离化合物相比，它可以到达整个淋巴结中更多的免疫细胞。释放速率可以编程，允许访问不同的淋巴结结构，因此可以访问特定的淋巴细胞亚群。因此，我们能够改变药物淋巴结细胞的亚型以提高免疫治疗效果。