Arsonoliposomes for the potential treatment of medulloblastoma.

Pharm Res

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

Published: October 2009

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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http://dx.doi.org/10.1007/s11095-009-9940-0DOI Listing

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