By taking advantage of the excessively upregulated expression of
neuropilin (NRP) on the surface of both
glioma cells and endothelial cells of angiogenic blood vessels, the
ligand of NRP with high affinity -
tLyp-1 peptide, which also contains a CendR motif ((R/K)XX(R/K)), was functionalized to the surface of
PEG-PLA nanoparticles (tLyp-1-NP) to mediate its
tumor homing, vascular extravasation and deep penetration into the
glioma parenchyma. The tLyp-1-NP was prepared via a
maleimide-
thiol coupling reaction with uniformly spherical shape under TEM and particle size of 111.30 ± 15.64 nm. tLyp-1-NP exhibited enhanced cellular uptake in both human umbilical vein endothelial cells and Rat C6
glioma cells, increased cytotoxicity of the loaded PTX, and improved penetration and growth inhibition in avascular C6
glioma spheroids. Selective accumulation and deep penetration of tLyp-1-NP at the
glioma site was confirmed by in vivo imaging and
glioma distribution analysis. The longest survival was achieved by those mice bearing intracranial C6
glioma treated with PTX-loaded tLyp-1-NP. The findings here strongly indicate that
tLyp-1 peptide-functionalized nanoparticulate DDS could significantly improve the efficacy of
paclitaxel glioma therapy.