Dual-Stimuli-Responsive Nanotheranostics for Dual-Targeting Photothermal-Enhanced Chemotherapy of Tumor.

Stimuli-responsive nanotheranostics have been widely explored for precision medicine. Here, we developed a pH/light dual-stimuli-responsive nanotheranostic agent for biological/physical dual-targeting photothermal-enhanced chemotherapy of U87MG tumor. This nanotheranostic agent was composed of the RGD (Arg-Gly-Asp) peptide, melanin-coated magnetic nanoparticles (MMNs), doxorubicin (DOX), and indocyanine green (ICG), denoted as RMDI. The tumor accumulation of RMDI was simultaneously improved through biological active targeting by RGD and physical magnetic targeting by an external magnetic field at tumor tissues, which was proven by in vivo photoacoustic/magnetic resonance/fluorescence (PA/MR/FL) trimodal imaging. Under dual stimuli of the tumor acidic microenvironment and laser irradiation, both DOX and ICG were released in a controlled fashion, demonstrating impressive therapeutic outcomes against U87MG tumor both in vitro and in vivo, respectively. Owing to the synergistic photothermal/chemotherapy, the dual-stimuli-responsive and dual-targeting nanotheranostic agent completely ablated U87MG tumor in vivo without any tumor recurrence and biotoxicity. This nanotheranostic agent exhibited great potential in multimodal imaging-guided synergistic therapy of cancer.