Imperial College London
Alternate

Professor Amin Hajitou

Faculty of Medicine, Department of Brain Sciences

Professor of Targeted Therapeutics
 
 
 
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Contact

 

+44 (0)20 7594 6546a.hajitou Website

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Tsafa:2020:10.3390/ijms21217867,
author = {Tsafa, E and Bentayebi, K and Topanurak, S and Yata, T and Przystal, J and Fongmoon, D and Hajji, N and Waramit, S and Suwan, K and Hajitou, A},
doi = {10.3390/ijms21217867},
journal = {International Journal of Molecular Sciences},
title = {Doxorubicin improves cancer cell targeting by filamentous phage gene delivery vectors.},
url = {http://dx.doi.org/10.3390/ijms21217867},
volume = {21},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Merging targeted systemic gene delivery and systemic chemotherapy against cancer, chemovirotherapy, has the potential to improve chemotherapy and gene therapy treatments and overcome cancer resistance. We introduced a bacteriophage (phage) vector, named human adeno-associated virus (AAV)/phage or AAVP, for the systemic targeting of therapeutic genes to cancer. The vector was designed as a hybrid between a recombinant adeno-associated virus genome (rAAV) and a filamentous phage capsid. To achieve tumor targeting, we displayed on the phage capsid the double-cyclic CDCRGDCFC (RGD4C) ligand that binds the alpha-V/beta-3 (αvβ3) integrin receptor. Here, we investigated a combination of doxorubicin chemotherapeutic drug and targeted gene delivery by the RGD4C/AAVP vector. Firstly, we showed that doxorubicin boosts transgene expression from the RGD4C/AAVP in two-dimensional (2D) cell cultures and three-dimensional (3D) tumor spheres established from human and murine cancer cells, while preserving selective gene delivery by RGD4C/AAVP. Next, we confirmed that doxorubicin does not increase vector attachment to cancer cells nor vector cell entry. In contrast, doxorubicin may alter the intracellular trafficking of the vector by facilitating nuclear accumulation of the RGD4C/AAVP genome through destabilization of the nuclear membrane. Finally, a combination of doxorubicin and RGD4C/AAVP-targeted suicide gene therapy exerts a synergistic effect to destroy human and murine tumor cells in 2D and 3D tumor sphere settings.
AU  - Tsafa,E
AU  - Bentayebi,K
AU  - Topanurak,S
AU  - Yata,T
AU  - Przystal,J
AU  - Fongmoon,D
AU  - Hajji,N
AU  - Waramit,S
AU  - Suwan,K
AU  - Hajitou,A
DO  - 10.3390/ijms21217867
PY  - 2020///
SN  - 1422-0067
TI  - Doxorubicin improves cancer cell targeting by filamentous phage gene delivery vectors.
T2  - International Journal of Molecular Sciences
UR  - http://dx.doi.org/10.3390/ijms21217867
UR  - http://hdl.handle.net/10044/1/84876
VL  - 21
ER  -
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