Fabrication And Functional Evaluation Of Prussian Blue Nanoagent For Cancer Diagnosis And Treatment

Cancer has become the major disease threat to human life worldwide. So far, the early detection and cure of cancer is still a big challenge. Recently, nanotechnology offers opportunities for the diagnosis and treatment of cancer. Because of the unique physical and chemical properties, avariety of nanomaterials can be used for effective diagnosis and treatment of cancer.Prussian blue(PB), a kind of ferrous ferricyanide composed of Fe2+ and Fe3+, has been approved by FDA as oral drug for the treatment of thallium and cesium.Existing studies show that Prussian blue nanomaterials with photothermal conversion performance, can be used as a new generation ofphotothermal agent for ablation of cancerous tumor.Based on the photothermaltherapeutic function of Prussian blue, this study is to design and prepare a series of Prussian blue nanoagents with improved functionsfor the diagnosis and treatment of cancer.Prussian blue nanoparticle(NPs) modified with hyaluronic acid grafting polyethylene glycol(HA-g-PEG) was fabricated. Result showed that PB/HA-g-PEGNPs can realize tumor targeting through the affinity of hyaluronic acid to CD44 receptor on cancer cells. Result showed that PB/HA-g-PEGNPs can be efficiently uptake by cancer cells through the CD44 receptor mediated active targeting. Cellullar experiments showed that PB/HA-g-PEGNPsenablean efficiently improved tumor-target PTT.For further improving the efficiency of cancer treatment base on PTT, we fabircated hollow PBNPs modified with HA-g-PEG, followed by loading 10-hydroxycamptothecin(HCPT) for tumor-targeted thermochemotherapy. The obtained nanoagent exhibited a great capability for targeting cancer cells over-expressing the CD44 receptor. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect.PB nanomaterials have strong absorption in the wavelength range from 650 to 1100 nm, thus this studyfor the first time found that PBNPs can be used as a contrast agents for photoacoustic imaging. Result showed that PBNPs can produce strong photoacoustic signal under 765 nm near infrared(NIR) laser pulse, and the photoacoustic imaging depth of PBNPs can be up to 4.3 cmin vitro. In vivo study showed that PBNPs can significantly enhance the contrast of cerebral cortex in mouse.Based on the CT imaging capability of gold nanoparticles and the photoacoustic imaging and photothermal therapeutic capabilities of Prussian blue nanoparticles, in this study, a Au/PB core-shell NPs(Au@PB NPs) were successfully designed. It was found that the Au@PB NPs has stronge photothermal effect, at the same time, possess the capability of photoacoustic and CT imaging. Tumor-bearing nude mice experiments show that the prepared Au@PB NPs make an effective combination of photoacoustic imaging and CT imaging, can accurately diagnose and locate tumor, and real-time guide the photothermal therapy(PTT).PB is a clinical medicine with high biological safety. Our study further improve the function of PB nanomaterials in photoacoustic imaging, imaging guided PTT of cancer, tumor-target PTT of cancer and tumor targeted thermochemotherapy. Our research further expand the function of Prussian blue in cancer diagnosis and treatment.