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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; in revised form: 10 January 2012 / Accepted: 12 January 2012 / Published: 16 January 2012
Abstract: 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.
Keywords: Quantum Dot; scFv; GRP78; nanoparticle; AKT; breast cancer
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MDPI and ACS Style
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.
Xu W, Liu L, Brown NJ, Christian S, Hornby D. Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice. Molecules. 2012; 17(1):796-808.
Xu, Weiming; Liu, Lizhi; Brown, Nicola J.; Christian, Sven; Hornby, David. 2012. "Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice." Molecules 17, no. 1: 796-808.