In situ phagocyte-mediated deep tumor penetration assisted by ApoA-1 mimetic peptide-modified silicasome

Deep tumor penetration of therapeutic drugs remains challenging for the ablation of solid tumors, which impedes their clinical translation. In situ cell-mediated delivery is an efficient strategy for deep drug tumor penetration. Herein, we designed a visible mesoporous silica nanoparticle (MSN) with indocyanine green (ICG) loading, lipid encapsulation and ApoA-1 mimetic peptide (R4F) modification, denoted R4F-ICG@L-MSN. The peripheral blood experiment and immunofluorescence reveal that with the aid of scavenger receptor class B type 1 (SR-B1) targeting ability, R4F-ICG@L-MSN could be specially transported by the in situ phagocyte-mediated delivery and efficiently taken up by 4T1 tumor cells and macrophages, achieving deep penetration and wide distribution in solid tumors. The visualized phototheranostic (photoacoustic imaging and photothermal therapy) verified that the deep tumor penetration of R4F-ICG@L-MSN enhance the efficiency of treatment for solid tumors, accompanied by the reversed immunosuppressive microenvironment. Such multifunctional R4F-ICG@L-MSN achieved tumor targeting, deep penetration, photoacoustic imaging-guided photothermal therapy and enhanced anti-tumor immune response, indicating advancements toward deep penetration in tumors and promoting effects for multimodality therapies.