Dual-Targeted Assembled\nNanodrugs for Near-Infrared\nPhotothermal Immunotherapy of Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is known for its\npoor prognosis\nand aggressive behavior, being highly prone to recurrence and metastasis,\nand currently has limited effective treatment options. Photothermal\ntherapy (PTT) is an emerging, minimally invasive, low-drug-resistance,\nand precisely controllable therapeutic method for cancer treatment,\noffering hope to break through the bottleneck in TNBC therapy. The\nantitumor efficiency of PTT is predominantly contingent upon the performance\nof the photothermal drugs. Therefore, there is an urgent need to develop\nphotothermal drugs that not only have excellent photothermal conversion\nefficiency but also possess strong tumor-targeting capabilities and\ngood biosafety. Here, we have developed a tumor-targeted photothermal\nagent with near-infrared (NIR) absorption capability based on the\nstrategy of biomolecular assembly, utilizing biliverdin manganese\ncomplexes (MnBV) and amphiphilic phospholipid–polymer conjugates\n(DSPE-PEG and DSPE-PEG-cKNGRE). This photothermal assembled drug exhibits\na uniform size, good stability, and ideal photothermal conversion\nefficiency. In the 4T1 tumor-bearing mouse model of TNBC, it shows\ngood tumor dual-targeting capabilities and a significant drug enrichment\nperformance. While ablating the primary tumor, PTT further stimulates\nthe maturation of dendritic cells (DCs), enhancing the infiltration\nof T lymphocytes into the spleen and tumor, thus reshaping the immune\nmicroenvironment of TNBC and thereby effectively inhibiting tumor\nmetastasis and recurrence. The developed photothermal assembled drug\nprovides an innovative candidate treatment paradigm for TNBC, offering\nthe potential to advance precise, targeted, and safe therapy for highly\ninvasive and aggressive malignancies.