Immunostimulant nanomodulator boosts antitumor immune response in triple negative breast cancer by synergism of vessel normalization and photothermal therapy

Tumor vascular dysfunction and immune suppression predict poor outcomes of tumor therapy. Combination of photothermal therapy (PTT) and vessel normalization with tumor immunotherapy is promising to augment antitumor benefit. Herein, we develop a potential immunostimulatory nanomodulator for treatment of triple-negative breast cancer (TNBC) treatment via synergism of PTT, vessel normalization, and priming of tumoral suppressive immune microenvironment by blocking transforming growth factor-β (TGF-β) pathway. The nanomodulator, namely Vac@Apt@BPs, is developed by conjugation of TGF-β inhibitor Vactosertib (Vac) and nucleolin-recognizing aptamer (Apt) on the surface of black phosphorus nanoparticles (BPs). Vac@Apt@BPs show good accumulation in TNBC via aptamer-induced active targeting of TNBC. Via the blockade of TGF-β signaling, Vac@Apt@BPs effectively inhibit the formation of tumor neovascular, and normalize the vessels to recover vascular integrity and alleviate the hypoxia stress. Together with the tumor eradication and immunogenic cell death via PTT, robust immune response was boosted by promoted maturation of dendritic cells, suppression of regulatory T cells, and stimulation of effective T cells. This synergistic therapeutic strategy potentially suppresses the growth of TNBC in mice.