The influence of the penetrating peptide iRGD on the effect of paclitaxel-loaded MT1-AF7p-conjugated nanoparticles on glioma cells.

摘要: Low permeability across the blood-brain tumor barrier (BTB) and poor penetration into glioma parenchyma represent key obstacles for anti-glioblastoma drug delivery. In this study, MT1-AF7p peptide, which presents high binding affinity to membrane type-1 matrix metalloproteinase (MT1-MMP) that over-expressed on both angiogenic blood vessels cells, was employed decorate paclitaxel-loaded PEG-PLA nanoparticles (MT1-NP-PTX) mediate glioblastoma targeting. Tumor-homing penetrating peptide iRGD co-administrated further facilitate extravasation from parenchyma. MT1-NP-PTX showed satisfactory encapsulated efficiency, loading capacity size distribution. C6 MT1-NP found exhibit significantly enhanced cellular accumulation than of unmodified NP via energy-dependent macropinocytosis lipid raft-mediated endocytosis. The anti-proliferative apoptosis-induction activity PTX following its encapsulation in MT1-NP. vivo imaging distribution together confirmed functionalization co-administration improved BTB Furthermore, vitro spheroid assays evidenced effectively penetrated spheroids growth inhibitory effects loaded spheroids. More importantly, median survival time those nude mice bearing intracranial received combination regimen 60 days, longer other groups. findings suggested BTB/glioma cells dual-targeting DDS with might provide a practical feasible solution highly efficient