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Recent progress has suggested that dual targeting drug delivery systems, which are functionalized with two active ligands targeting the blood brain barrier (BBB) and brain tumor cells respectively, provide a promising strategy to improve the chemotherapeutic efficacy for gliomas. The key to successfully developing such systems is to functionalize nanoparticles (NPs) with active ligands, though they usually suffer from several issues such as NP aggregation, drug leakage and complicated chemical synthesis. Herein we report a facile way of constructing a dual targeting delivery system by simply using lipid capped polymer NPs. The NPs were constructed with a poly lactic-co-glycolic acid (PLGA) core for hydrophobic doxorubicin (DOX) loading, and a lipid (lecithin and DSPE–PEG2000–COOH) shell. The DSPE–PEG2000–COOH provides an excellent anchor for ligand conjugation. As a proof of concept, two active ligands of angiopep-2 peptide and AS1411 aptamer were covalently linked to NPs through a single step synthesis, with little effect on particle size, stability, drug loading and drug release performance. The accumulative drug release of the NPs in PBS (pH 7.4) over 144 h is ∼50%, suggesting a sustained drug release profile. The NPs showed significantly enhanced uptake by brain capillary endothelial cells (BCECs) and C6 glioma cells as indicated by fluorescence microscopy and quantitative flow cytometry, demonstrating the dual targeting efficiency. The BBB penetration ability is validated by using an in vitro BBB model, and the in vitro cell inhibition study showed increased cytotoxicity of the NPs to glioma cells.

Facile construction of dual-targeting delivery system by using lipid capped polymer nanoparticles for anti-glioma therapy