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Arsonoliposomes for the Potential Treatment of Medulloblastoma

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ABSTRACT

Purpose

To investigate the arsonoliposome effect on medulloblastoma cells (VC312Rs) related to uptake, endocytotic mechanism and cell viability.

Methods

VC312R viability in presence of either arsonoliposomes or stealth liposomes was studied using MTT assay for 1–4 days. Fibroblasts (3T3) were used as control. Apoptosis was studied for 2 h, 5 h and 24 h. Bodipy-labelled arsonoliposome uptake (time- and dose-dependent) was estimated using FACS analysis. The endocytotic mechanism was investigated using inhibitors of clathrin- (chlorpromazine) and caveolae-mediated endocytosis (filipin).

Results

Arsonoliposomes affected significantly the VC312R viability compared to 3T3 cells and induced apoptosis to VC312Rs after 2 h of incubation. Apoptosis was not observed for 3T3 cells. Liposome uptake versus time showed a bimodal pattern. Clathrin-mediated endocytosis was the main endocytotic mechanism at low lipid concentrations and caveolae at higher ones; thus, dose-dependent uptake did not show a plateau at increased lipid concentrations.

Conclusions

Arsonoliposomes showed “selective” toxicity towards medulloblastoma cells inducing apoptosis after 2 hs of incubation. Therefore, arsonoliposomes are promising anticancer vehicles for brain tumour treatment.

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Abbreviations

ABB:

annexin binding buffer

Bodipy:

boron-dipyrromethene

C16-As:

2,3-dipalmitoyloxypropylarsonic acid

Chol:

cholesterol

CPZ:

chlorpromazine hydrochloride

DAPI:

4′,6-diamidino-2-phenylindole

DHPE:

1,2-dihexadecanoyl-SN-glycero-3-phosphoethanolamine

DMSO:

dimethylsulfoxide

DSPC:

1,2-distearoyl-sn-glycero-3-phosphocholine

FACS:

fluorescence-activated cell sorting

FBS:

fetal bovine serum

MEM:

minimum essential medium

PBS:

phosphate buffer saline

PFA:

paraformaldehyde

PI:

propidium iodide

PS:

phosphatidyl serine

Rhod:

rhodamine

SUPW:

sterile ultra pure water

TNF-α:

tumoural necrosis factor

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ACKNOWLEDGEMENTS

Authors express their gratitude to Prof. Geoffrey J. Pilkington (School of Pharmacy and Biomedical Sciences, University of Portsmouth) for the kind donation of VC312R cells, Dr. Adrian Robins and Nina Lane (University of Nottingham) for their invaluable help with the FACS analysis, and Iain Ward (University of Nottingham) for his technical support on the confocal microscope. This project is part of a Ph.D. thesis funded by Medway School of Pharmacy, University of Kent/Greenwich, Kent, UK.

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Authors and Affiliations

  1. Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK

    Marco E. Favretto & Paraskevi Kallinteri

  2. School of Biomedical Science, University of Nottingham, Nottingham, NG72RD, UK

    Showan Marouf & Terence L. Parker

  3. Department of Chemistry and School of Pharmacy, University of Patras, Rio, Patras, 26504, Greece

    Panagiotis Ioannou & Sophia G. Antimisiaris

Authors
  1. Marco E. Favretto
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  2. Showan Marouf
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  3. Panagiotis Ioannou
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  4. Sophia G. Antimisiaris
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  5. Terence L. Parker
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  6. Paraskevi Kallinteri
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Correspondence to Paraskevi Kallinteri.

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Favretto, M.E., Marouf, S., Ioannou, P. et al. Arsonoliposomes for the Potential Treatment of Medulloblastoma. Pharm Res 26, 2237–2246 (2009). https://doi.org/10.1007/s11095-009-9940-0

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  • DOI: https://doi.org/10.1007/s11095-009-9940-0

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