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.

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.

Burn conversion is a contributor to morbidity that currently has no quantitative measurement system. Active dynamic thermography (ADT) has recently been characterized for the early assessment of burn wounds and resolves the three-dimensional structure of materials by heat transfer analysis. As conversion is a product of physiological changes in three-dimensional structure, with subsequent modification of heat transfer properties, the authors hypothesize that ADT can specifically identify the process of burn conversion and serve as an important tool for burn care. A heated comb was used to create four contact burns separated by three interspaces on bilateral flanks of 18 rats, resulting in 144 burns and 108 interspaces. Wounds were imaged by ADT and laser Doppler imaging (LDI) pre- and post-injury through hour 36, with a subset undergoing biopsy collection. Direct analysis of thermographic and perfusion data revealed an increasing difference between burns and interspaces by ADT with increasing injury severity (P < .05), while LDI characterized the opposite. Comparison of stasis zones to burns reveals the ability of ADT to distinguish these two regions in both intermediate and deep burns at every assessment (P < .05). In addition, when wounds are grouped as converting or not converting, ADT identifies by hour 12, wounds that will convert (P < .05). LDI identifies by hour 4 wounds that will not (P < .05). This study has demonstrated that ADT can directly identify burn wound conversion, while LDI can identify nonconverting wounds. Further advancement of ADT technology has the potential to guide real-time interventional techniques.

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Active dynamic thermography (ADT) is an imaging technique capable of characterizing the non-homogenous thermal conductance of damaged tissues. The purpose of this study was to determine optimal stimulation parameters and quantify the optical resolution of ADT through various depths of human skin. Excised tissue from plastic surgery operations was collected immediately following excision. A total of 12 thin to thick split-thickness grafts were harvested from 3 patients. Grafts were placed on top of a 3D printed resolution chart and thermal stimulation was applied from a 300W halogen lamp array for between 0.5-10 seconds to determine optimal parameters. Video was captured with a thermal camera, and analysis was performed by reconstructing an image from thermal gradients. In this study ADT resolved 0.445±0 lp/mm at a depth of 0.010", 0.356±0.048 lp/mm at a depth of 0.015", 0.334±0.027 lp/mm at a depth of 0.020" and 0.265±0.022 lp/mm at a depth of 0.025". The stimulus energy required for maximum resolution at each depth was 3-4s, 8s, 12s and 12s respectively. ADT is a sensitive technique for imaging dermal structure, capable of resolving detail as fine as 1124 μm, 1427 μm, 1502 μm and 1893 μm in thin to thick split-thickness skin grafts respectively. This study has characterized a correlation between stimulus input and maximal resolution at differing depths of skin. It has also defined the functional imaging depth of ADT to below the sub-cutis, well below conventional spectrophotometric techniques.

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