In vivo Tumor Targeting and Imaging with Ocean Nanocrystals
Ocean NanoTech’s nanocrystals were used in the development of epidermal growth factor receptor (EGFR) targeted nanoparticles. The QD EGFR targeted nanoparticles are developed by conjugating a single-chain anti-EGFR antibody (ScFvEGFR) to surface functionalized quantum dots (QDs) or magnetic iron oxide (IO) nanoparticles. The results showed that ScFvEGFR can be successfully conjugated to the nanoparticles, resulting in compact ScFvEGFR nanoparticles that specifically bind to and are internalized by EGFR-expressing cancer cells producing a fluorescent signal or magnetic resonance imaging (MRI) contrast. In vivo tumor targeting and uptake of the nanoparticles in human cancer cells is demonstrated after systemic delivery of ScFvEGFR-QDs or ScFvEGFR-IO nanoparticles into an orthotopic pancreatic cancer model. Therefore, ScFvEGFR nanoparticles have potential to be used as a molecular-targeted in vivo tumor imaging agent.
Efficient internalization of ScFvEGFR nanoparticles into tumor cells after systemic delivery suggests that the EGFR-targeted nanoparticles can also be used for the targeted delivery of therapeutic agents. By using a high-affinity single-chain anti-EGFR antibody and nanoparticles, a compact-sized, EGFR-targeted nanoparticles for in vivo tumor imaging and delivery of therapeutic agents was developed. We showed that the ScFvEGFR nanoparticles specifically bound to EGFR, a cell surface receptor that is expressed in high percentage by human tumor cells. The EGFR-mediated internalization of the targeted nanoparticles in tumor cells increased the retention time and amount of the nanoparticles inside the tumor mass. Both of these properties fit very well with the criteria for molecular receptor-targeted tumor imaging. It was also shown that ScFvEGFR conjugated nanoparticles were stable, retain target specificity to EGFR expressing tumor cells, and enabled EGFR-targeted MRI of human pancreatic cancer orthotopically implanted in the pancreas of nude mice. The studies demonstrated the potential applications of ScFvEGFR-conjugated nanoparticles for the detection of EGFR-expressing tumors using in vivo imaging approaches.
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* Lily Yang, Hui Mao, Y. Andrew Wang, Zehong Cao, Xianghong Peng, Xiaoxia Wang,Hongwei Duan, Chunchun Ni, Qingan Yuan, Gregory Adams, Mark Q. Smith, William C. Wood, Xiaohu Gao, and Shuming Nie, “Single Chain Epidermal Growth Factor Receptor Antibody Conjugated Nanoparticles for in vivo Tumor Targeting and Imaging,” Small, 5 (2), 235-243, 2009.