Novel Prussian Blue Analogue Nanostructures Mediated Theranostics For Breast Cancer

Part Ⅰ Hybrid Au-star@Prussian Blue for High-Performance towards Bimodal Imaging and Photothermal TreatmentPhotothermal therapy (PTT) nanomaterials hold the potential of ablation cancer cells or tissues through conversion of near-infrared (NIR) light into thermal energy, has been increasingly investigated. However, there are still chances in strategies that can further enhance photo conversion efficiency and improve photothermal tumor ablation effect of current nanomaterials. The advanced hybrid nanoparticles for on demand diagnostics and therapeutics of diseases have rapidly constructed in nanomedicine. Branched or star-shaped Au nanostructures consisting of a core and protruding arms have recently received particular interest due to their unique morphology and optical properties. Prussian blue (PB) as a clinically adapted agent recently has drawn much attention in cancer theranostics for potential applications in magnetic resonance (MR) imaging as well as photothermal cancer treatment. Here we fabricate a novel hybrid, star-shaped Au nanostructure coated with PB (Au-star@PB,～100 nm in size), precisely engineered to remarkably amplify photoacoustic (PA) imaging signals and photothermal efficiency. Both T1-weighted MR imaging and PA signal showed high accumulation of Au-star@PB after injection in the tumor region.Single intratumor injection of Au-star@PB followed by low power density 808 nm laser irradiation (0.82 W cm-2,3 min) revealed effective inhibition of tumor growth due to the photothermal therapies.With enhanced performance of photothermal therapeutic efficiency and the characteristic of each agent, these hybrid nanoparticles have the potential for clinical translation to treat solid cancer where tumors accessible by NIR laser.Part Ⅱ A Multifunctional PB@mSiO2-PEG/DOX Nanoplatform for Combined Photothermal-Chemotherapy of TumorIn this work, prussian blue nanocubes are first coated with mesoporous silica and then modified with PEG to construct multifunctional PB@mSiO2-PEG nanocubes. The PB@mSiO2-PEG nanocubes have good biocompatibility, excellent photo-thermal transformation capacity, in vivo magnetic resonance and photoacoustic imaging ability. After loading antitumor drug doxorubicin (DOX) in the PB@mSiO2-PEG nanocubes, the constructured PB@mSiO2-PEG/DOX nanoplatforms show an excellent pH-responsive drug release character, viz an ultra-low cumulative drug release amount of 3.1% at pH 7.4 within 48 h and a high release amount of 46.6% at pH 5.0. Upon near-infrared laser irradiation, the PB@mSiO2-PEG/DOX nanoplatforms show an enhanced synergistic photothermal and chemical therapeutic efficacy for breast cancer than solo photothermal therapy or chemotherapy.Part Ⅲ Redox-derived Formation of Hollow Ag@HPB Nanoparticles for Repeated Photo-thermal PropertiesThe metal-organic framework (MOF) is of great interest owing to its fascinating applications such as adsorption/desorption and photothermal therapy. Prussian blue nanoparticle (PB NPs), one of the most ancient MOFs, has been developed with an unexpected method. Redox-etching reactions have been successfully realized by etching newly-formed cubic AgNPs into small AgNPs and diffused in the structure of PB while maintaining its hollow structure (Ag@HPB NPs). TEM images indicated that the Ag@HPB were highly uniformed nanocubes, with hollow structure at an average diameter of 76 nm. And Ag@HPB NPs have a strong NIR absorption at the wavelength of 756 nm. Besides, Ag@HPB NP exhibit good performance of MR and PA imaging. In particular, as a photo-absorption material in glue media inherently integrates the photo-thermal absorption, Ag@HPB NPs has demonstrated high potential of theranostics for tumors.