Tuning the Organ Tropism of Polymersome for Spleen‐Selective Nanovaccine Delivery to Boost Cancer Immunotherapy

Abstract The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non‐specific distribution in non‐targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, a general strategy that enables tuning the tropism of polymersomes for liver‐ and spleen‐selective delivery is reported. By using a library screening approach, spleen‐targeted polymersome PH9‐Aln‐8020 and liver‐targeted polymersome PA9‐ZP3‐5050 are identified accordingly. Meanwhile, the second near‐infrared (NIR‐II) fluorescence imaging allows for in vivo dynamic evaluation of their spatial and temporal accumulation in specific tissues. O ur findings indicate that both polymer composition and protein corona on the surface are essential to determine the in vivo fate of polymersomes and tendency for specific organs. Importantly, PH9‐Aln‐8020 is employed as a systemic nanocarrier to co‐deliver the antigen and adjuvant, which remarkably boost splenic immune responses in acute myeloid leukemia, melanoma, and melanoma lung metastasis mouse models. This study may open a new frontier for polymersomes in organ‐selective delivery and other biomedical applications.