We describe Prussian blue nanoparticles (PB NPs) for laser-induced photothermal therapy (PTT) of tumors. The PB NPs exhibit strong absorbance at near infrared (NIR) wavelengths, are stable, non-toxic, and have 20.5% photothermal conversion efficiencies. PTT with PB NPs in a mouse model of neuroblastoma resulted in marked tumor debulking, increased tumor-free days, and decreased tumor growth rates in tumor-bearing mice. These findings demonstrate the clinical potential of PB NPs for PTT of tumors.

Recent evidence shows that neuroinflammation plays a role in many neurological diseases including mild cognitive impairment (MCI) and Alzheimer's disease (AD), and that free water (FW) modeling from clinically acquired diffusion MRI (DTI-like acquisitions) can be sensitive to this phenomenon. This FW index measures the fraction of the diffusion signal explained by isotropically unconstrained water, as estimated from a bi-tensor model. In this study, we developed a simple but powerful whole-brain FW measure designed for easy translation to clinical settings and potential use as a priori outcome measure in clinical trials. These simple FW measures use a “safe” white matter (WM) mask without gray matter (GM)/CSF partial volume contamination (WMsafe) near ventricles and sulci. We investigated if FW inside the WMsafe mask, including and excluding areas of white matter damage such as white matter hyperintensities (WMHs) as shown on T2 FLAIR, computed across the whole white matter could be indicative of diagnostic grouping along the AD continuum. After careful quality control, 81 cognitively normal controls (NC), 103 subjects with MCI and 42 with AD were selected from the ADNIGO and ADNI2 databases. We show that MCI and AD have significantly higher FW measures even after removing all partial volume contamination. We also show, for the first time, that when WMHs are removed from the masks, the significant results are maintained, which demonstrates that the FW measures are not just a byproduct of WMHs. Our new and simple FW measures can be used to increase our understanding of the role of inflammation-associated edema in AD and may aid in the differentiation of healthy subjects from MCI and AD patients.

Core/shell and core/shell/shell particles comprised of the Prussian blue analogues K(j)Ni(k)[Cr(CN)(6)](l)·nH(2)O (A) and Rb(a)Co(b)[Fe(CN)(6)](c)·mH(2)O (B) have been prepared for the purpose of studying persistent photoinduced magnetization in the heterostructures. Synthetic procedures have been refined to allow controlled growth of relatively thick (50-100 nm) consecutive layers of the Prussian blue analogues while minimizing the mixing of materials at the interfaces. Through changes in the order in which the two components are added, particles with AB, ABA, BA, and BAB sequences have been prepared. The two Prussian blue analogues were chosen because B is photoswitchable, and A is ferromagnetic with a relatively high magnetic ordering temperature, ~70 K, although it is not known to exhibit photoinduced changes in its magnetic properties. Magnetization measurements on the heterostructured particles performed prior to irradiation show behavior characteristic of the individual components. On the other hand, after irradiation with visible light, the heterostructures undergo persistent photoinduced changes in magnetization associated with both the B and A analogues. The results suggest that structural changes in the photoactive B component distort the normally photoinactive A component, leading to a change in its magnetization.

Heterostructured thin films consisting of distinct layers of the Prussian blue analogues Rb a Co b [Fe(CN)6] c ·mH2O (CoFe PBA) and Rb j M k [Cr(CN)6] l ·nH2O (MCr PBA, where M = Ni or Co) have been fabricated, and their photomagnetic properties have been investigated. The CoFe PBA is known to be photoactive, with light induced changes in the unit cell size and the spin states below ∼150 K and magnetic order below ∼20 K. The NiCr and CoCr PBAs do not have native photoeffects, but are known to have higher magnetic ordering temperatures (T C NiCr ∼ 70 K, T C CoCr ∼ 30 K), and a pressure dependence of the magnetization. The layered heterostructures are synthesized using aqueous chemistry and sequential adsorption techniques that allow for fine control of layer thickness. Some of the heterostructured films show photoinduced magnetization changes up to the ordering temperatures of the MCr PBA component, behavior that is not seen when the individual materials are measured separately. A variety of different layer arrangements and thicknesses has been investigated with the goal of identifying structures that optimize the photocontrol of the magnetic response in the MCr PBA lattices, which are in intimate contact with the photoactive CoFe PBA lattices. The new behavior is optimized when the constituent layers have thicknesses on the order of hundreds of nanometers. When layers are too thin, it is shown that mixing of ions at the interface between PBA components leads to mixed-metal phases. The concurrence of the maximum temperature of the large photomagnetic effect with the native ordering temperature of the MCr PBA lattice, as well as its magnetic field dependence, supports the interpretation that the photocontrol is the result of photoinduced structural changes in the CoFe PBA lattice coupling to the MCr PBA component of the heterostructure, inducing random magnetic anisotropy.

Molecular imaging agents enable the visualization of phenomena with cellular and subcellular level resolutions and therefore have enormous potential in improving disease diagnosis and therapy assessment. In this article, we describe the synthesis, characterization, and demonstration of core-shell, biofunctionalized, gadolinium-containing Prussian blue nanoparticles as multimodal molecular imaging agents. Our multimodal nanoparticles combine the advantages of MRI and fluorescence. The core of our nanoparticles consists of a Prussian blue lattice with gadolinium ions located within the lattice interstices that confer high relaxivity to the nanoparticles providing MRI contrast. The relaxivities of our nanoparticles are nearly nine times those observed for the clinically used Magnevist. The nanoparticle MRI core is biofunctionalized with a layer of fluorescently labeled avidin that enables fluorescence imaging. Biotinylated antibodies are attached to the surface avidin and confer molecular specificity to the nanoparticles by targeting cell-specific biomarkers. We demonstrate our nanoparticles as multimodal molecular imaging agents in an in vitro model consisting of a mixture of eosinophilic cells and squamous epithelial cells. Our nanoparticles specifically detect eosinophilic cells and not squamous epithelial cells, via both fluorescence imaging and MRI in vitro. These results suggest the potential of our biofunctionalized Prussian blue nanoparticles as multimodal molecular imaging agents in vivo.