Liposomes Combined an Integrin α<sub>v</sub>β<sub>3</sub>‑Specific Vector with pH-Responsible Cell-Penetrating Property for Highly Effective Antiglioma Therapy through the Blood–Brain Barrier
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Abstract
Glioma,
one of the most common aggressive malignancies, has the
highest mortality in the present world. Delivery of nanocarriers from
the systemic circulation to the glioma sites would encounter multiple
physiological and biological barriers, such as blood–brain
barrier (BBB) and the poor penetration of nanocarriers into the tumor.
To circumvent these hurdles, the paclitaxel-loaded liposomes were
developed by conjugating with a TR peptide (PTX-TR-Lip), integrin
α<sub>v</sub>β<sub>3</sub>-specific vector with pH-responsible
cell-penetrating property, for transporting drug across the BBB and
then delivering into glioma. Surface plasmon resonance (SPR) studies
confirmed the very high affinity of TR-Lip and integrin α<sub>v</sub>β<sub>3</sub>. In vitro results showed that TR-Lip exhibited
strong transport ability across BBB, killed glioma cells and brain
cancer stem cells (CSCs), and destroyed the vasculogenic mimicry (VM)
channels. In vivo results demonstrated that TR-Lip could better target
glioma, and eliminated brain CSCs and the VM channels in tumor tissues.
The median survival time of tumor-bearing mice after administering
PTX-TR-Lip (45 days) was significantly longer than that after giving
free PTX (25.5 days, <i>p</i> < 0.001) or other controls.
In conclusion, PTX-TR-Lip would improve the therapeutic efficacy of
brain glioma in vitro and in vivo