Targeting of α _ν β ₃ -Integrins Expressed on Tumor Tissue and Neovasculature Using Fluorescent Small Molecules and Nanoparticles

Abstract

Aims-Receptor-specific small molecules and nanoparticles are widely used in molecular imaging of tumors. Although some studies have described the relative strengths and weaknesses of the two approaches, reports of a direct comparison and analysis of the two strategies are lacking. Herein, we compared the tumor targeting characteristics of a small near-infrared (NIR) fluorescent compound (cypate -peptide conjugate) and a relatively large perfluorocarbon-based nanoparticles (250 nm diameter) for imaging α ν β 3 -integrin receptor expression in tumors.Materials and Methods-NIR fluorescent small molecules and nanoparticles were administered to living mice bearing subcutaneous or intradermal syngeneic tumors and imaged with whole-body and high resolution optical imaging systems.Results-The nanoparticles, designed for vascular constraint, remained within the tumor vasculature while the small integrin-avid ligand diffused into tissue to target integrin expression NIH Public Access Author ManuscriptNanomedicine (Lond). Author manuscript; available in PMC 2011 July 1. Conclusions-Fluorescent small molecular probes show greater overall early tumor contrast and rapid visualization of tumors, but the vascular-constrained nanoparticles are more selective for detecting cancer-induced angiogenesis. A combination of both imaging agents provides a strategy to image and quantify integrin expression in tumor tissue and tumor-induced neovascular system.

Noninvasive Photoacoustic and Fluorescence Sentinel Lymph Node Identification using Dye-Loaded Perfluorocarbon Nanoparticles

“…The synthesis and optical properties of these dyes (absorption, emission and FLT) were reported previously 23, 28, 29. Both dyes possess high molar absorptivity in NIR range >200,000 M −1 cm −1 .…”

“…Both dyes possess high molar absorptivity in NIR range >200,000 M −1 cm −1 . Cypate-C18 has a moderate fluorescence quantum yield and a relatively short FLT due to the flexible excited state structure 23, 30. In contrast, PPCy-C8 with its highly rigid skeleton ensured by complexation with disubstituted boron possesses high fluorescence quantum yield and much longer FLT (Table 1).…”

“…A hydrophobic derivative of cypate,32 cypate-C18,23 and diketopyrrolopyrrole cyanine, PPCy-C833 were synthesized as previously described. PFC nanoparticles with both hydrophobic dyes were formulated as previously described23 with the addition of NIR fluorescent dyes for optical and PA imaging.…”

Perfluorocarbon nanoemulsions with fluorescent, colloidal and magnetic properties

“…Also, no reports exist where PCE was used for drug and/or dye delivery where these are introduced into the internal phase of nanoemulsion. Rather, in earlier reports of PCE nanoemulsions aimed at drug delivery, the surfactant layer incorporated the drug, dye or a targeting agent [24,29,36–38]. The rationale behind PCE/hydrocarbon 1:1 v/v ratio is to increase delivery capacity of the PCE nanoemulsion, providing enough hydrocarbon oil to solubilize a water-insoluble dye (or drug) while the PCE content is kept at sufficiently high level for future in vivo 19 F MRI.…”

“…The overall chemical environment of the NIR dye when incorporated into the PFC nanoemulsions will impact its fluorescence properties and photostability. NIR dyes are commonly introduced into the PFC nanoemulsions by either incorporation into the surfactant layer [23,24] or droplet surface conjugation [25]. In either approach, there is a possibility of dissociation of the NIR dye from the PFC nanodroplet due to chemical degradation mechanisms or colloidal destabilization.…”