This study describes the previously unreported intrinsic capacity of poly-
L-lysine (PLL) sixth generation (G(6))
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.