Arsonoliposomes for the Potential Treatment of Medulloblastoma

• Published in: Pharmaceutical research Vol. 26; no. 10; pp. 2237 - 2246
• Main Authors: Favretto, Marco E, Marouf, Showan, Ioannou, Panagiotis, Antimisiaris, Sophia G, Parker, Terence L, Kallinteri, Paraskevi
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.10.2009; Springer US; Springer; Springer Nature B.V
• Subjects: 3T3 Cells; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Apoptosis; Arsenicals - administration & dosage; Arsenicals - pharmacokinetics; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Brain cancer; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Cellular biology; Dose-Response Relationship, Drug; Drug Delivery Systems - methods; Endocytosis - physiology; General pharmacology; Liposomes; Medical Law; Medical sciences; Medulloblastoma - drug therapy; Medulloblastoma - metabolism; Mice; Original Article; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Toxicity; Treatment Outcome; arsonoliposomes; apoptosis; liposomes; medulloblastoma; cellular uptake; Nervous system diseases; Pharmaceutical technology; Liposome; Malignant tumor; In vitro; Uptake; Cerebral disorder; Treatment; Cell death; Medulloblastoma; Central nervous system disease; Cancer; Apoptosis
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-009-9940-0

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.