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.