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Molecules 2012, 17(1), 796-808;

Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice

Department of Molecular Biology and Biotechnology, The Krebs Institute, The University of Sheffield, S10 2TN, UK
Academic Surgical Oncology Unit, Department of Oncology, Faculty of Medicine, Dentistry and Health, University of Sheffield, S10 2RX, UK
Bayer Pharma AG, BSP-GDD-GTR-TD-TR2W, Aprather Weg 18a, 2096 Wuppertal, Germany
Author to whom correspondence should be addressed.
Received: 13 December 2011 / Revised: 10 January 2012 / Accepted: 12 January 2012 / Published: 16 January 2012
(This article belongs to the Section Molecular Diversity)
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Semiconductor quantum dots (Qdots) have recently been shown to offer significant advantages over conventional fluorescent probes to image and study biological processes. The stability and low toxicity of QDs are well suited for biological applications. Despite this, the potential of Qdots remains limited owing to the inefficiency of existing delivery methods. By conjugating Qdots with small antibody fragments targeting membrane-bound proteins, such as GRP78, we demonstrate here that the Quantum dot- Anti-GRP78 scFv (Qdot-GRP78) retains its immunospecificity and its distribution can be monitored by visualization of multi-color fluorescence imaging both in vitro and in vivo. Moreover we demonstrate here for the first time that Qdot-GRP78 scFv bioconjugates can be efficiently internalized by cancer cells, thus upregulate phophosphate-AKT-ser473 and possess biological anti-tumour activity as shown by inhibition of breast cancer growth in a xenograft model. This suggests that nanocarrier-conjugated scFvs can be used as a therapeutic antibody for cancer treatment. View Full-Text
Keywords: Quantum Dot; scFv; GRP78; nanoparticle; AKT; breast cancer Quantum Dot; scFv; GRP78; nanoparticle; AKT; breast cancer

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Xu, W.; Liu, L.; Brown, N.J.; Christian, S.; Hornby, D. Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice. Molecules 2012, 17, 796-808.

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