Hybrid Gd3+ /cisplatin cross-linked polymer nanoparticles enhance platinum accumulation and formation of DNA adducts in glioblastoma cell lines

Biomaterials Science
Hélène LajousEmmanuel Garcion

Abstract

Glioblastoma is the most frequent and aggressive primary malignant tumor of the central nervous system with a gloomy prognosis. Platinum derivatives and one among them, cisplatin, exhibited promising results when locally administered into the brain of glioblastoma bearing rats. Nanovectorization of anticancer agents through polymeric nanoparticles may even promote drug accumulation within cells, thus concentrating the drug efficiently at its target. Anchorage of gadolinium complexes on the corona of such smart drug delivery systems could further allow magnetic resonance imaging (MRI) monitoring of the nanoplatform biodistribution in the damaged parenchyma and its therapeutic benefit. For this purpose, a biocompatible amphiphilic triblock copolymer, made of degradable polyester and polycarbonate and bioeliminable polyethylene oxide (PEO), was synthesized by successive ring-opening polymerizations. After micellization in water, gadolinium complexes were grafted onto the PEO micelle corona and the carboxylate functions, located at the surface of the micelle's core, were able to cross-link with Pt(ii) complexes. A macromolecular prodrug was therefore recovered in which more than one third of the carboxylate functions were linked to...Continue Reading

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Citations

Aug 8, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xiaoli WuJin Chang
Apr 14, 2019·Trends in Pharmacological Sciences·Hélène LajousEmmanuel Garcion
Jun 11, 2021·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Tao TangTaolei Sun

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Methods Mentioned

BETA
X-ray
imaging technique
NMR
Dynamic Light Scattering
Size
Size Exclusion Chromatography
FCS

Software Mentioned

GraphPad Prism
NTA
Malvern Zetasizer
ParaVision

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