Water-Soluble DOX·HCl Delivery Nanoplatform for Efficient Photothermal Therapy with Chemotherapy: Polydopamine and Mesoporous Silica-Coated Gold Nanorods

Combination therapies of photothermal therapy with chemotherapy have demonstrated considerable potential for enhancing the efficacy of cancer treatment due to chemical-sensitizing effects. Therein, water-soluble chemotherapeutic drugs have good therapeutic prospects, but their undesirable release properties need to be addressed. In this study, a novel nanoplatform was developed based on a gold nanorod core and mesoporous silica shell, modified with a polydopamine surface layer and loaded with doxorubicin hydrochloride (DOX·HCl), denoted as DOX·HCl/AuNR@MSN-PDA. The nanoplatform was designed to achieve controlled and rapid release of the hydrophilic chemosensitizer while enabling effective photothermal therapy. The rod-shaped nanostructure exhibited excellent photothermal stability and had a diameter of approximately 85 nm. The water-soluble drug DOX·HCl was efficiently loaded into the mesoporous channels through a combination of shielding and π-π stacking interactions with the PDA shell, yielding a drug loading capacity of 13.6%. The nanoplatform also displayed pH-responsive release behavior with a cumulative DOX·HCl release of 66% under weakly acidic conditions (pH 5.0). Furthermore, near-infrared (NIR) irradiation enhanced the release by an additional 10% over 24 h. Cytotoxicity assays revealed that DOX·HCl/AuNR@MSN-PDA under NIR irradiation exhibited stronger antitumor activity than free DOX·HCl, underscoring the synergistic effect of photothermal therapy with chemotherapy within the tumor microenvironment.