Photothermal treatment of prostate tumor with micellar indocyanine green and napabucasin to co-ablate cancer cells and cancer stem cells.

Advanced prostate cancer is hassled by relapse and metastasis that are closely associated with cancer stem cells (CSCs). Here, we present micellar indocyanine green and napabucasin (mICG-Nap) that co-ablates cancer cells and CSCs via photothermal therapy (PTT) for the treatment of prostate tumor. mICG-Nap with stable loading of both drugs and favorable size effectively reduced CSC population in RM1-PSMA murine prostate cancer cells and inhibited tumor spheroid formation. mICG-Nap showed an enhanced photothermal effect compared with free ICG and eliminated tumor spheroids under near-infrared (NIR) irradiation. The efficacy of mICG-Nap was further enhanced by decorating with Acupa ligand, which targets to RM1-PSMA cells and tumors via PSMA receptor. The enhanced tumor cell uptake of Acupa-mICG-Nap led to significant survival benefits in both subcutaneous RM1-PSMA tumor models and postoperative models. The tumor analyses demonstrated clear downregulation of CSC-related biomarkers such as OCT4, SOX2, CD133 and pSTAT3 as well as PSMA by Acupa-mICG-Nap. Rational formulated micellar indocyanine green and napabucasin plus NIR appears as an appealing strategy to co-ablate cancer cells and CSCs with rapid tumor de-bulking yet no recurrence.