Glioma homing peptide-modified PEG-PCL nanoparticles for enhanced anti-glioma therapy

Peptide-mediated drug delivery system (DDS) has been increasingly used to promote on-demand treatment efficacy of cancers. Herein, LTLRWVGLMS (LS10) peptide is selected as the functional ligand for specific glioma-targeting drug delivery. LS10 peptide selectively binds to NG2 proteins that are widely overexpressed in the glioma cells and restricted in normal tissue. LS10 peptide-decorated DDS is expected to hold vast promises in glioma therapy and decrease unwanted side effects.

LS10 peptide was conjugated on the surface of poly(ethylene glycol)-poly(ɛ-caprolactone) (PEG-PCL) nanoparticles via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride/N-hydroxysulfosuccinimide coupling reaction. Using U87MG cells as the glioma cell model, cellular uptake, internalization mechanism, cellular cytotoxicity and apoptosis were investigated. 1,1'-Dioctadecyl-3,3,3',3'-tetramethyl indotricarbocyanine iodide were used as fluorescence probes to investigated in vivo glioma targeting capability of LS10-NP. The glioma therapeutic efficacy of paclitaxel-loaded LS10-NP was studied on glioma-bearing nude mice.

The LS10-NP with size of 119 nm enhanced cellular uptake on U87MG cells, increased cytotoxicity of the loaded paclitaxel (PTX), and improved penetration in 3D U87MG glioma spheres. In vivo biodistribution experiments showed that LS10-NP exhibited the enhanced drug localization at glioma site, which resulted in prolonged survival time of glioma-bearing mice.

Our results indicated that LS10 peptide-modified nanoparticulate DDS could significantly improve the anti-glioma efficacy.