Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy

Amit K Singh,1,2 Megan A Hahn,2 Luke G Gutwein,3 Michael C Rule,4 Jacquelyn A Knapik,5 Brij M Moudgil,1,2 Stephen R Grobmyer,3 Scott C Brown,2,61Department of Materials Science and Engineering, College of Engineering, 2Particle Engineering Research Center, College of Engineering, 3Division of Surgical Oncology, Department of Surgery, College of Medicine, 4Cell and Tissue Analysis Core, McKnight Brain Institute, 5Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; 6DuPont Central Research and Development, Corporate Center for Analytical Science, Wilmington, DE, USABackground: Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology.Methods: We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallo-naphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model.Results: The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (>110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis.Conclusion: MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.Keywords: bioluminescence, in vivo imaging, mesoporous silica nanoparticles, NIR fluorescence, photothermal ablation, theranostic