Core–Satellite Mesoporous Silica–Gold Nanotheranostics for Biological Stimuli Triggered Multimodal Cancer Therapy

A core–satellite nanotheranostic agent with pH-dependent photothermal properties, pH-triggered drug release, and H₂O₂-induced catalytic generation of radical medicine is fabricated to give a selective and effective tumor medicine with three modes of action. The nanocomplex (core–satellite mesoporous silica–gold nanocomposite) consists of amino-group-functionalized mesoporous silica nanoparticles (MSN-NH₂) linked to L-cysteine-derivatized gold nanoparticles (AuNPs-Cys) with bridging ferrous iron (Fe²⁺) ions. The AuNPs-Cys serve as both removable caps that control drug release (doxorubicin) and stimuli-responsive agents for selective photothermal therapy. Drug release and photothermal therapy are initiated by the cleavage of Fe²⁺ coordination bonds at low pH and the spontaneous aggregation of the dissociated AuNPs-Cys. In addition, the Fe²⁺ is able to catalyze the decomposition of hydrogen peroxide abundant in cancer cells by a Fenton-like reaction to generate high-concentration hydroxyl radicals (·OH), which then causes cell damage. This system requires two tumor microenvironment conditions (low pH and considerable amounts of H₂O₂) to trigger the three therapeutic actions. In vivo data from mouse models show that a tumor can be completely inhibited after two weeks of treatment with the combined chemo-photothermal method; the data directly demonstrate the efficiency of the MSN–Fe–AuNPs for tumor therapy.