A Triple-Collaborative Strategy for High-Performance Tumor Therapy by Multifunctional Mesoporous Silica-Coated Gold Nanorods

摘要

To integrate treatments of photothermal therapy, photodynamic therapy (PDT), and chemotherapy, this study reports on a multifunctional nanocomposite based on mesoporous silica-coated gold nanorod for high-performance oncotherapy. Gold nanorod core is used as the hyperthermal agent and mesoporous silica shell is used as the reservoir of photosensitizer (Al(III) phthalocyanine chloride tetrasulfonic acid, AlPcS4). The mesoporous silica shell is modified with -cyclodextrin (-CD) gatekeeper via redox-cleavable Pt(IV) complex for controlled drug release. Furthermore, tumor targeting ligand (lactobionic acid, LA) and long-circulating poly(ethylene glycol) chain are introduced via host-guest interaction. It is found that the nanocomposite can specifically target to hepatoma cells by virtue of the LA targeting moiety. Due to the abundant existence of reducing agents within tumor cells, -CD can be removed by reducing the Pt(IV) complex to active cisplatin drug for chemotherapy, along with the releasing of entrapped AlPcS4 for effective PDT. As confirmed by in vitro and in vivo studies, the nanocomposite exhibits an obvious near-infrared induced thermal effect, which significantly improves the PDT and chemotherapy efficiency, resulting in a superadditive therapeutic effect. This collaborative strategy paves the way toward high-performance nanotherapeutics with a superior antitumor efficacy and much reduced side effects.