Dual-Targeted Assembled Nanodrugs for Near-Infrared Photothermal Immunotherapy of Triple-Negative Breast Cancer

Abstract

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