Publications
2010
Al-Jamal Khuloud T, Al-Jamal Wafa’ T, Akerman Simon, Podesta Jennifer E, Yilmazer Açelya, Turton John A, Bianco Alberto, Vargesson Neil, Kanthou Chryso, Florence Alexander T, Tozer Gillian M, Kostarelos Kostas
Systemic antiangiogenic activity of cationic poly-L-lysine dendrimer delays tumor growth Article de journal
Dans: Proceedings of the National Academy of Sciences, vol. 107, no. 9, p. 3966–3971, 2010, ISSN: 0027-8424, 1091-6490.
Résumé | Liens | BibTeX | Étiquettes: angiogenesis, cancer, I2CT, nanoparticle, Team-Bianco
@article{al-jamal_systemic_2010,
title = {Systemic antiangiogenic activity of cationic poly-L-lysine dendrimer delays tumor growth},
author = {Khuloud T Al-Jamal and Wafa’ T Al-Jamal and Simon Akerman and Jennifer E Podesta and Açelya Yilmazer and John A Turton and Alberto Bianco and Neil Vargesson and Chryso Kanthou and Alexander T Florence and Gillian M Tozer and Kostas Kostarelos},
url = {https://www.pnas.org/content/107/9/3966},
doi = {10.1073/pnas.0908401107},
issn = {0027-8424, 1091-6490},
year = {2010},
date = {2010-03-01},
urldate = {2020-04-01},
journal = {Proceedings of the National Academy of Sciences},
volume = {107},
number = {9},
pages = {3966--3971},
abstract = {This study describes the previously unreported intrinsic capacity of poly-L-lysine (PLL) sixth generation (G6) dendrimer molecules to exhibit systemic antiangiogenic activity that could lead to solid tumor growth arrest. The PLL-dendrimer-inhibited tubule formation of SVEC4-10 murine endothelial cells and neovascularization in the chick embryo chick chorioallantoic membrane (CAM) assay. Intravenous administration of the PLL-dendrimer molecules into C57BL/6 mice inhibited vascularisation in Matrigel plugs implanted subcutaneously. Antiangiogenic activity was further evidenced using intravital microscopy of tumors grown within dorsal skinfold window chambers. Reduced vascularization of P22 rat sarcoma implanted in the dorsal window chamber of SCID mice was observed following tail vein administration (i.v.) of the PLL dendrimers. Also, the in vivo toxicological profile of the PLL-dendrimer molecules was shown to be safe at the dose regime studied. The antiangiogenic activity of the PLL dendrimer was further shown to be associated with significant suppression of B16F10 solid tumor volume and delayed tumor growth. Enhanced apoptosis/necrosis within tumors of PLL-dendrimer-treated animals only and reduction in the number of CD31 positive cells were observed in comparison to protamine treatment. This study suggests that PLL-dendrimer molecules can exhibit a systemic antiangiogenic activity that may be used for therapy of solid tumors, and in combination with their capacity to carry other therapeutic or diagnostic agents may potentially offer capabilities for the design of theranostic systems.},
keywords = {angiogenesis, cancer, I2CT, nanoparticle, Team-Bianco},
pubstate = {published},
tppubtype = {article}
}
This study describes the previously unreported intrinsic capacity of poly-L-lysine (PLL) sixth generation (G6) dendrimer molecules to exhibit systemic antiangiogenic activity that could lead to solid tumor growth arrest. The PLL-dendrimer-inhibited tubule formation of SVEC4-10 murine endothelial cells and neovascularization in the chick embryo chick chorioallantoic membrane (CAM) assay. Intravenous administration of the PLL-dendrimer molecules into C57BL/6 mice inhibited vascularisation in Matrigel plugs implanted subcutaneously. Antiangiogenic activity was further evidenced using intravital microscopy of tumors grown within dorsal skinfold window chambers. Reduced vascularization of P22 rat sarcoma implanted in the dorsal window chamber of SCID mice was observed following tail vein administration (i.v.) of the PLL dendrimers. Also, the in vivo toxicological profile of the PLL-dendrimer molecules was shown to be safe at the dose regime studied. The antiangiogenic activity of the PLL dendrimer was further shown to be associated with significant suppression of B16F10 solid tumor volume and delayed tumor growth. Enhanced apoptosis/necrosis within tumors of PLL-dendrimer-treated animals only and reduction in the number of CD31 positive cells were observed in comparison to protamine treatment. This study suggests that PLL-dendrimer molecules can exhibit a systemic antiangiogenic activity that may be used for therapy of solid tumors, and in combination with their capacity to carry other therapeutic or diagnostic agents may potentially offer capabilities for the design of theranostic systems.