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Glioma homing peptide-modified PEG-PCL nanoparticles for enhanced anti-glioma therapy.
- Source :
-
Journal of drug targeting [J Drug Target] 2016; Vol. 24 (3), pp. 224-32. Date of Electronic Publication: 2015 Jul 29. - Publication Year :
- 2016
-
Abstract
- Background: 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.<br />Methods: 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.<br />Results: 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.<br />Conclusion: Our results indicated that LS10 peptide-modified nanoparticulate DDS could significantly improve the anti-glioma efficacy.
- Subjects :
- Animals
Apoptosis drug effects
Cell Line, Tumor
Ethylene Glycols administration & dosage
Ethylene Glycols pharmacokinetics
Glioma metabolism
Male
Mice
Mice, Nude
Paclitaxel administration & dosage
Paclitaxel therapeutic use
Particle Size
Peptides pharmacokinetics
Polyesters administration & dosage
Polyesters pharmacokinetics
Tissue Distribution
Drug Delivery Systems methods
Ethylene Glycols chemistry
Glioma drug therapy
Nanoparticles administration & dosage
Nanoparticles chemistry
Peptides administration & dosage
Peptides chemistry
Polyesters chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2330
- Volume :
- 24
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of drug targeting
- Publication Type :
- Academic Journal
- Accession number :
- 26219518
- Full Text :
- https://doi.org/10.3109/1061186X.2015.1070854