Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy.
BACKGROUND
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.


CONCLUSIONS
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.
Department of Materials Science and Engineering, College of Engineering, University of Florida, Gainesville, FL 32610, USA.
Amit K
AK
Singh
Megan A
MA
Hahn
Luke G
LG
Gutwein
Michael C
MC
Rule
Jacquelyn A
JA
Knapik
Brij M
BM
Moudgil
Stephen R
SR
Grobmyer
Scott C
SC
Brown
D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology*; D006651:Histocytochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy*; D012822:Silicon Dioxide / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
D002232:Carbocyanines; D005456:Fluorescent Dyes; D012822:Silicon Dioxide