Hierarchical HAp–AuNR hybrid microspheres as pH/NIR sensitive drug carrier for photothermal/chemo synergic therapy

To integrate pH/NIR dual-responsive drug release mechanisms with multimodal therapies for effective treatment of malignant tumors, hierarchical hydroxyapatite (HAp)/AuNR hybrid microspheres, consisting of a hollow HAp core and an AuNR shell, were facilely synthesized using phytic acid (IP6) as a sustainable template and phosphorus source. Urea served as the pore-forming agent and pH regulator during the synthesis process. The integration of AuNR into multifunctional HAp systems enabled NIR-responsive controllable drug release and photothermal ablation specifically at the tumorigenic site. The aggregation of AuNR within and outside the hybrid microspheres effectively hinders the release of doxorubicin hydrochloride (DOX) from the hollow HAp microspheres, mitigating the initial burst release and minimizing side effects. The results indicate that the h-HAp/AuNR hybrid exhibited remarkable drug loading efficiency (159.9 μ g ⋅ mg − 1 ), with drug release exhibiting pH-dependent behavior due to the dissolution of HAp in acidic environments. Furthermore, MTT assays and fluorescence imaging demonstrate that DOX-loaded h-HAp/AuNR significantly enhance antitumor efficacy, achieving a cell survival rate of 12.3% at a concentration of 100 μ g ⋅ mL. This integrated system offers a promising approach for combined chemotherapeutic delivery and NIR photothermal therapy.