Photothermal-based combination therapy using functional nanomaterials shows great promise in eradication of aggressive tumors and improvement of drug sensitivity. The therapeutic efficacy and adverse effects of drug combinations depend on the precise control of timely tumor-localized drug release. Here a polymer-dopamine nanocomposite is designed for combination therapy, thermo-responsive drug release and prevention of uncontrolled drug leakage. The thermo-sensitive co-polymer poly (2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate)-co-2-(dimethylamino) ethyl methacrylate-b-poly (D, l-lactide-co-glycolide) is constructed into core-shell structured nanoparticles for co-encapsulation of two cytotoxic drugs and absorption of small interfering RNAs against survivin. The drug-loaded nanoparticles are surface-coated with polydopamine which confers the nanoformulation with photothermal activity and protects drugs from burst release. Under tumor-localized laser irradiation, polydopamine generates sufficient heat, resulting in nanoparticle collapse and instant drug release within the tumor. The combination strategy of photothermal, chemo-, and gene therapy leads to triple-negative breast cancer regression, with a decrease in the chemotherapeutic drug dosage to about 1/20 of conventional dose. This study establishes a powerful nanoplatform for precisely controlled combination therapy, with dramatic improvement of therapeutic efficacy and negligible side effects.

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