CD44-Targeted Gold-Nanorod-Based Nano-adjuvant Combining Mild Photothermal Therapy and Immune Activation for Triple-Negative Breast Cancer Therapy

Triple-negative breast cancer (TNBC) poses a significant therapeutic challenge due to its aggressive nature, lack of targetable receptors, and resistance to conventional treatments. To address this, we developed a CD44-targeted gold-based nanoadjuvant (RGSA) combining mild photothermal therapy (mPTT) and immune activation for enhanced antitumor immunity. The system consists of mesoporous silica-coated gold nanorods (GmS) functionalized with hyaluronic acid (HA) to promote tumor-selective accumulation. Under near-infrared (NIR) irradiation, RGSA generates localized hyperthermia (<45 °C), inducing immunogenic cell death (ICD) while sparing healthy tissue. Simultaneously, it enables tumor microenvironment-responsive release of the TLR7 agonist R837, boosting dendritic cell maturation and cytotoxic T cell infiltration. In orthotopic TNBC models, RGSA-mediated therapy achieved complete tumor regression, suppressed metastasis, and reversed immunosuppression without systemic toxicity. This work demonstrates a spatiotemporally controlled photothermal-immunotherapy approach to transform immunologically "cold" TNBC into "hot" tumors, offering a translatable alternative to conventional therapies.