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

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 li...

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Detalles Bibliográficos
Autores principales: Xu, Weiming, Liu, Lizhi, Brown, Nicola J., Christian, Sven, Hornby, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268310/
https://www.ncbi.nlm.nih.gov/pubmed/22249409
http://dx.doi.org/10.3390/molecules17010796
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author Xu, Weiming
Liu, Lizhi
Brown, Nicola J.
Christian, Sven
Hornby, David
author_facet Xu, Weiming
Liu, Lizhi
Brown, Nicola J.
Christian, Sven
Hornby, David
author_sort Xu, Weiming
collection PubMed
description 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.
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spelling pubmed-62683102018-12-11 Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice Xu, Weiming Liu, Lizhi Brown, Nicola J. Christian, Sven Hornby, David Molecules Article 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. MDPI 2012-01-16 /pmc/articles/PMC6268310/ /pubmed/22249409 http://dx.doi.org/10.3390/molecules17010796 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Xu, Weiming
Liu, Lizhi
Brown, Nicola J.
Christian, Sven
Hornby, David
Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice
title Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice
title_full Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice
title_fullStr Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice
title_full_unstemmed Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice
title_short Quantum Dot- Conjugated Anti-GRP78 scFv Inhibits Cancer Growth in Mice
title_sort quantum dot- conjugated anti-grp78 scfv inhibits cancer growth in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268310/
https://www.ncbi.nlm.nih.gov/pubmed/22249409
http://dx.doi.org/10.3390/molecules17010796
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