Osteotropic Polypeptide Nanoparticles with Dual hydroxyapatite Binding Properties and Controlled Cisplatin Delivery
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Nanoparticles with prolonged residence time in bone constitute a valuable strategy for bone disease treatments. The aim of this work was to synthesise a simple nanoparticulate system exhibiting both anticancer and hydroxyapatite binding properties for potential bone cancer applications.
The amphiphilic copolymer poly(γ-benzyl-glutamate)-block-poly(glutamic acid) (PBLG-b-PGlu) was synthetised by ring opening polymerization and nanoparticles were obtained by a simple nanoprecipitation method. Nanoparticles were characterized in terms of cisplatin interaction, association, and release as well as interaction with hydroxyapatite and their cytoxicity was studied in three prostate cancer cell lines.
PBLG-b-PGlu nanoparticles of ~50 nm in size were successfully prepared. They could display for the first time dual hydroxyapatite binding and anticancer properties mediated by the PGlu moiety. They could complex cisplatin at a drug loading content of 6.2% (w/w). Cisplatin release was triggered by physiological concentrations of chloride ions according to an almost zero order kinetics during 14 days. Simultaneously, these nanoparticles showed in vitro hydroxyapatite binding. Finally, they were shown to exert a cytotoxic effect in three prostate cancer cell lines that potentially metastasize to bone.
These properties suggest the potential utility of cisplatin-loaded PBLG-b-PGlu nanoparticles as carrier systems for the treatment of bone metastases.
KEY WORDScisplatin hydroxyapatite nanoparticles poly(benzylglutamate) poly(glutamic acid)
Atomic absorption spectroscopy
Dynamic light scattering
Degree of polymerization
Fourier transform infrared spectroscopy
- H NMR
Proton nuclear magnetic resonance
Isothermal titration calorimetry
([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4 sulfophenyl)-2H tetrazolium, inner salt)
Phosphate buffer saline
Ring opening polymerization
Size exclusion chromatography
Transmission Electron Microscopy
ACKNOWLEDGMENTS AND DISCLOSURES
We gratefully acknowledge the European postgraduate program from “Ibercaja Foundation” for the financial support of Laura de Miguel. This work has benefited from the facilities and expertise of the Platform for Transmission Electronic Microscopy of IMAGIF (Centre de Recherche de Gif - www.imagif.cnrs.fr) and we thank Miss Cynthia Gillet for her valuable help with the TEM image acquisitions. We thank Dr Silvia Mazzaferro and LCPO, Univ. Bordeaux, CNRS, UMR 5629 for the SEC analyses.
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