Transition-metal dyshomeostasis is recognized as a critical pathogenic factor at the onset and progression of neurodegenerative disorder (ND). Excess transition-metal ions such as Cu can catalyze the generation of cytotoxic reactive oxygen species and thereafter induce neuronal cell apoptosis. Exploring new chelating agents, which are not only capable of capturing excess redox-active metal, but can also cross the blood-brain barrier (BBB), are highly desired for ND therapy. Herein, it is demonstrated that 2D black phosphorus (BP) nanosheets can capture Cu efficiently and selectively to protect neuronal cells from Cu -induced neurotoxicity. Moreover, both in vitro and in vivo studies show that the BBB permeability of BP nanosheets is significantly improved under near-infrared laser irradiation due to their strong photothermal effect, which overcomes the drawback of conventional chelating agents. Furthermore, the excellent biocompatibility and stability guarantee the biosafety of BP in future clinical applications. Therefore, these features make BP nanosheets have the great potential to work as an efficient neuroprotective nanodrug for ND therapy.

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Current nanodrug-based cancer therapy is susceptible to the problems of rapid clearance from circulation and limited therapeutic efficacy. Herein, we report a magnetically targeted and photothermal-triggered drug release nanotheranostics system based on superparamagnetic iron oxide (Fe3O4), IR780, doxorubicin (DOX), and perfluoropentane (PFP) entrapped poly-lactide-co-glycolide (PLGA) nanoparticles (IR780/Fe3O4@PLGA/PFP/DOX NPs) for triple-modal imaging-guided synergistic therapy of breast cancer. In this work, IR780 and Fe3O4 convert light into heat, which triggers DOX release from IR780/Fe3O4@PLGA/PFP/DOX NPs and a phase-shift thermoelastic expansion of PFP; this procedure further accelerates the DOX release and tissue extrusion deformation. Fe3O4 NPs also serve as the target moiety by an external magnet directed to the tumor. Specifically, the IR780/Fe3O4@PLGA/PFP/DOX NPs can be used for triple-modal imaging, including near infrared fluorescence, magnetic resonance, and ultrasound. Furthermore, the antitumor therapy studies reveal the extraordinary performance of IR780/Fe3O4@PLGA/PFP/DOX NPs in magnetically targeted synergistic chemo-photothermal therapy of cancer. Therefore, the multifunctional IR780/Fe3O4@PLGA/PFP/DOX NPs guided by the magnetic field show a great potential for cancer theranostics.

Near-infrared (NIR) laser-induced photothermal therapy (PTT) uses a photothermal agent to convert optical energy into thermal energy and has great potential as an effective local, minimally invasive treatment modality for killing cancer cells. To improve the efficacy of PTT, we developed poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) encapsulating superparamagnetic iron oxide (Fe3O4), indocyanine green (ICG), and perfluoropentane (PFP) as synergistic agents for NIR laser-induced PTT. We fabricated a novel type of phase-shifting fluorescent magnetic NPs, Fe3O4/ICG@PLGA/PFP NPs, that effectively produce heat in response to NIR laser irradiation for an enhanced thermal ablation effect and a phase-shift thermoelastic expansion effect, and thus, can be used as a photothermal agent. After in vitro treatment of MCF-7 breast cancer cells with Fe3O4/ICG@PLGA/PFP NPs and NIR laser irradiation, histology and electron microscopy confirmed severe damage to the cells and the formation of many microbubbles with iron particles at the edge or outside of the microbubbles. In vivo experiments in mice with MCF-7 tumors demonstrated that Fe3O4/ICG@PLGA/PFP NPs could achieve tumor ablation upon NIR laser irradiation with minimal toxicity to non-irradiated tissues. Together, our results indicate that Fe3O4/ICG@PLGA/PFP NPs can be used as effective nanotheranostic agents for tumor ablation.