Cellular uptake and in vitro antitumor efficacy of composite liposomes for neutron capture therapy

Radiation Oncology

Peter Langguth¹  Thomas Nawroth¹  Gabriele Hampel³  Dorothee Iffland³  Christian Schütz³  Markus Ziegner²  Matthias Blaickner²  Catrin Grunewald³  Tanja Peters¹ 

[1] Institute of Pharmacy and Biochemistry, Department of Biopharmaceutics and Pharmaceutical Technology, Johannes Gutenberg University Mainz, Staudingerweg 5, Mainz, D-55128, Germany;AIT Austrian Institute of Technology, Health & Environment Department, Biomedical Systems, Donau-City-Strasse 1/2, Vienna, A-1220, Austria;Institute of Nuclear Chemistry, Johannes Gutenberg University Mainz, Fritz-Strassmann Weg 6, Mainz, D-55128, Germany

关键词: Theranostic;    Glioma;    Neutron capture therapy;    Drug uptake;    Liposomes;    Gadolinium;   

Others  :  1139717
DOI  :  10.1186/s13014-015-0342-7

 received in 2014-07-02, accepted in 2015-01-29,  发布年份 2015

【 摘 要 】

Background

Neutron capture therapy for glioblastoma has focused mainly on the use of ¹⁰B as neutron capture isotope. However, ¹⁵⁷Gd offers several advantages over boron, such as higher cross section for thermal neutrons and the possibility to perform magnetic resonance imaging during neutron irradiation, thereby combining therapy and diagnostics. We have developed different liposomal formulations of gadolinium-DTPA (Magnevist®) for application in neutron capture therapy of glioblastoma. The formulations were characterized physicochemically and tested in vitro in a glioma cell model for their effectiveness.

Methods

Liposomes entrapping gadolinium-DTPA as neutron capture agent were manufactured via lipid/film-extrusion method and characterized with regard to size, entrapment efficiency and in vitro release. For neutron irradiation, F98 and LN229 glioma cells were incubated with the newly developed liposomes and subsequently irradiated at the thermal column of the TRIGA reactor in Mainz. The dose rate derived from neutron irradiation with ¹⁵⁷Gd as neutron capturing agent was calculated via Monte Carlo simulations and set in relation to the respective cell survival.

Results

The liposomal Gd-DTPA reduced cell survival of F98 and LN229 cells significantly. Differences in liposomal composition of the formulations led to distinctly different outcome in cell survival. The amount of cellular Gd was not at all times proportional to cell survival, indicating that intracellular deposition of formulated Gd has a major influence on cell survival. The majority of the dose contribution arises from photon cross irradiation compared to a very small Gd-related dose.

Conclusions

Liposomal gadolinium formulations represent a promising approach for neutron capture therapy of glioblastoma cells. The liposome composition determines the uptake and the survival of cells following radiation, presumably due to different uptake pathways of liposomes and intracellular deposition of gadolinium-DTPA. Due to the small range of the Auger and conversion electrons produced in ¹⁵⁷Gd capture, the proximity of Gd-atoms to cellular DNA is a crucial factor for infliction of lethal damage. Furthermore, Gd-containing liposomes may be used as MRI contrast agents for diagnostic purposes and surveillance of tumor targeting, thus enabling a theranostic approach for tumor therapy.

【 授权许可】

   
2015 Peters et al.; licensee BioMed Central.

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