Multifunctional
Tandem Peptide Modified Paclitaxel-Loaded
Liposomes for the Treatment of Vasculogenic Mimicry and Cancer Stem
Cells in Malignant Glioma
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Abstract
The chemotherapy of aggressive glioma
is usually accompanied by
a poor prognosis because of the formation of vasculogenic mimicry
(VM) and brain cancer stem cells (BCSCs). VM provided a transporting
pathway for nutrients and blood to the extravascular regions of the
tumor, and BCSCs were always related to drug resistance and the relapse
of glioma. Thus, it is important to evaluate the inhibition effect
of antiglioma drug delivery systems on both VM and BCSCs. In this
study, paclitaxel-loaded liposomes modified with a multifunctional
tandem peptide R8-c(RGD) (R8-c(RGD)-Lip) were used for the treatment
of glioma. An in vitro cellular uptake study proved the strongest
targeting ability to be that of R8-c(RGD)-Lip to glioma stem cells.
Drug loaded R8-c(RGD)-Lip exhibited an efficient antiproliferation
effect on BCSCs and could induce the destruction of VM channels in
vitro. The following pharmacodynamics study demonstrated that R8-c(RGD)-modified
drug-loaded liposomes achieved both anti-VM and anti-BCSC effects
in vivo. Finally, no significant cytotoxicity of the blood system
or major organs of the drug-loaded liposomes was observed under treatment
dosage in the safety evaluation. In conclusion, all of the results
proved that R8-c(RGD)-Lip was a safe and efficient antiglioma drug
delivery system