Peptide-conjugated polymeric micellar nanoparticles for Dual SPECT and optical imaging of EphB4 receptors in prostate cancer xenografts

Abstract EphB4, a member of the largest family of receptor tyrosine kinases, is overexpressed in numerous tumors. In this study, we developed a new class of multimodal nanoplatform for dual single photon emission computed tomography (SPECT) and near-infrared fluorescence imaging of EphB4. EphB4-bind...

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Bibliographic Details
Published in:Biomaterials 2011-09, Vol.32 (25), p.5872-5879
Main Authors: Zhang, Rui, Xiong, Chiyi, Huang, Miao, Zhou, Min, Huang, Qian, Wen, Xiaoxia, Liang, Dong, Li, Chun
Format: Article
Language:English
Subjects:
Advanced Basic Science
Cell Line, Tumor
Dentistry
Fluorescence
Humans
Male
Micelle
Micelles
Molecular imaging
Nanoparticle
Nanoparticles
Peptides - chemistry
Polymers - chemistry
Prostatic Neoplasms - physiopathology
Receptor, EphB4 - analysis
Tomography, Emission-Computed, Single-Photon
Transplantation, Heterologous
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Summary:Abstract EphB4, a member of the largest family of receptor tyrosine kinases, is overexpressed in numerous tumors. In this study, we developed a new class of multimodal nanoplatform for dual single photon emission computed tomography (SPECT) and near-infrared fluorescence imaging of EphB4. EphB4-binding peptide TNYL-FSPNGPIARAW (TNYL-RAW) was conjugated to polyethylene glycol-coated, core-crosslinked polymeric micelles (CCPM) dually labeled with near-infrared fluorescence fluorophores (Cy7) and a radioisotope (indium 111). In vitro , TNYL-RAW-CCPM selectively bound to EphB4-positive PC-3M prostate cancer cells, but not to EphB4-negative A549 lung cancer cells. In vivo, PC-3M tumors were clearly visualized by both SPECT and near-infrared fluorescence tomography after intravenous administration of111 In-labeled TNYL-RAW-CCPM. In contrast, there was little signal in A549 tumors of mice injected with111 In-labeled TNYL-RAW-CCPM or in PC-3M tumors of mice injected with111 In-labeled CCPM. The high accumulation of111 In-labeled TNYL-RAW-CCPM in PC-3M tumor could be significantly reduced after co-injection with an excess amount of TNYL-RAW peptide. Immunohistochemical analysis showed that fluorescence signal from the nanoparticles correlated with their radioactivity count, and co-localized with the EphB4 expressing region.111 In-labeled TNYL-RAW-CCPM allowed visualization of cancer cells overexpressing EphB4 by both nuclear and optical techniques. The complementary information acquired with multiple imaging techniques should be advantageous in early detection of cancer.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2011.04.070