Chemotherapy failure of
glioma, the most aggressive and devastating
cancer, might be ascribed to the physiologic barriers of the
tumor mainly including heterogeneous
tumor perfusion and vascular permeability, which result in a limited penetration of chemotherapeutics. Besides, the vasculogenic mimicry (VM) channels, which are highly resistant to anti-angiogenic
therapy and serve as a
complement of angiogenesis, were abound in
glioma and always associated with
tumor recurrence. In order to enhance the
therapy effect of anti-
glioma, we developed a
PEG-PLA-based nanodrug delivery system (nanoparticles, NP) in this study and modified its surface with CK
peptide, which was composed of a human sonic hedgehog (SHH) targeting
peptide (CVNHPAFAC) and a KDR targeting
peptide (K237) through a GYG linker, for facilitating efficient VM channels,
tumor neovasculature, and
glioma cells multi-targeting delivery of
paclitaxel. In vitro cellular assay showed that CK-NP-PTX not only exhibited the strongest antiproliferation effect on U87MG cells and HUVEC cells but also resulted in the most efficient destruction of VM channels when compared with CVNHPAFAC-NP, K237-NP, and the unmodified ones. Besides, CK-NP accumulated more selectively at the
glioma site as demonstrated by in vivo and ex vivo imaging. As expected, the
glioma-bearing mice treated with CK-NP-PTX achieved the longest median survival time compared to those treated with CVNHPAFAC-NP-PTX and K237-NP-PTX. These findings indicated that the multi-targeting
therapy mediated by CK
peptide might provide a promising way for
glioblastoma therapy.