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In order to solve the problems of receptor promiscuity and poor blood-brain barrier (BBB) penetration in the treatment of glioblastomas (GBM), a novel dual-functional nanocomplex drug delivery system is developed based on the strategy of peptide-drug conjugates. In this study, SynB3-PVGLIG-PTX is designed and screened out by matrix metalloproteinase-2 (MMP-2), to which it exhibits the best affinity. The MMP-2-sensitive peptide (PVGLIG) and a cell-penetration peptide (SynB3) are combined to form a dual-functional peptide. Moreover, as a drug-peptide nanocomplex, SynB3-PVGLIG-PTX exhibited a high potential to form an aggregation with good solubility that can release paclitaxel (PTX) through the cleavage of MMP-2. From a functional perspective, it is found that SynB3-PVGLIG-PTX can specifically inhibit the proliferation, migration, and invasion of GBM cells in vitro in the presence of MMP-2, in contrast to that observed in MMP-2 siRNA transfected cells. Further investigation in vivo shows that SynB3-PVGLIG-PTX easily enters the brain of U87MG xenograft nude mice and can generate a better suppressive effect on GBM through a controlled release of PTX from SynB3-PVGLIG-PTX compared with PTX and temozolomide. Thus, it is proposed that SynB3-PVGLIG-PTX can be used as a novel drug-loading delivery system to treat GBM due to its specificity and BBB permeability.
Pubmed ID: 33552853
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