Tumor neovasculature and
tumor cells dual-targeting
chemotherapy can not only destroy the
tumor neovasculature, cut off the supply of nutrition and starve the
tumor cells, but also directly kill
tumor cells, holding great potential in overcoming the drawbacks of anti-angiogenic
therapy only and improving the anti-
glioma efficacy. In the present study, by taking advantage of the specific expression of
fibronectin extra domain B (EDB) on both
glioma neovasculature endothelial cells and
glioma cells, we constructed EDB-targeted
peptide APTEDB-modified
PEG-PLA nanoparticles (
APT-NP) for
paclitaxel (PTX) loading to enable
tumor neovasculature and
tumor cells dual-targeting
chemotherapy. PTX-loaded
APT-NP showed satisfactory encapsulated efficiency, loading capacity and size distribution. In human umbilical vein endothelial cells,
APT-NP exhibited significantly elevated cellular accumulation via energy-dependent, caveolae and
lipid raft-involved endocytosis, and improved PTX-induced apoptosis therein. Both in vitro tube formation assay and in vivo
matrigel angiogenesis analysis confirmed that
APT-NP significantly improved the antiangiogenic ability of PTX. In U87MG cells,
APT-NP showed elevated cellular internalization and also enhanced the cytotoxicity of the loaded PTX. Following
intravenous administration, as shown by both in vivo live animal imaging and tissue distribution analysis,
APT-NP achieved a much higher and specific accumulation within the
glioma. As a result,
APT-NP-PTX exhibited improved anti-
glioma efficacy over unmodified nanoparticles and
Taxol(®) in both subcutaneous and intracranial U87MG xenograft models. These findings collectively indicated that APTEDB-modified nanoparticles might serve as a promising nanocarrier for
tumor cells and neovasculature dual-targeting
chemotherapy and hold great potential in improving the efficacy anti-
glioma therapy.