Veicolazione selettiva a cellule umane di neuroblastoma di [125I]-metaiodiobenzilguanidina mediata da immunoliposomi anti-GD2

Translated title of the contribution: Selective delivery of [125I]- metaiodobenzilguanidine to neuroblastoma cells by anti-GD2 immunoliposomes

C. Brignole, G. Pagnan, F. Pastorino, E. Cosimo, S. Ferrando, L. Raffaghello, P. G. Montaldo, M. Ponzoni

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Delivery of anticancer drugs in sterically stabilized immunoliposomes (SIL) is an emerging tool for the selective somministration of antitumor agents to cells expressing specific antigens. Neuroblastoma (NB) cells, as well as some neuroectoderma-derived cell lineages, such as melanoma cells, express frequently disialoganglioside GD2. We thus explored the feasibility to encapsulate the radiometabolic drug iodine-labelled-metaiodobenzilguanidine (125I-MIBG) into anti-GD2 immunoliposomes and investigated the cellular uptake and metabolism of SIL-MIBG compared to free MIBG into NB and melanoma cells in vitro. Methods We successfully loaded free 125I-MIBG into stabilized liposomes and covalently coupled them to monoclonal anti-GD2 antibodies. The relative expression of MIBG-transporter and GD2 determined the degree of MIBG uptake. Results Uptake of SIL-encapsulated MIBG by all GD2-positive cell lines tested was higher than that of free MIBG. Moreover, successful incorporation of MIBG in melanoma cells, which are inherently non competent in taking up the free drug, could be achieved by SIL-MIBG. In contrast MIBG uptake was not observed into GD2-negative cells by treatment with SIL-MBG. Interestingly, the intracellular half-life of SIL-MIBG was significantly more prolonged than that of free MIBG in all NB cell lines, which reportedly cannot efficiently store free MIBG in subcellular compartments. The retention of SIL-MIBG by NB and melanoma cells was similar to that observed with free MIBG in highly storage-efficient pheochromocytoma (PC) cells. Conclusions Targeting GD2-positive cells with specific MIBG-loaded immunoliposomes appears a novel strategy for tumor cell killing, regardless of their competence to specifically incorporate the free compound.

Translated title of the contributionSelective delivery of [125I]- metaiodobenzilguanidine to neuroblastoma cells by anti-GD2 immunoliposomes
Original languageItalian
Pages (from-to)217-225
Number of pages9
JournalRivista Italiana di Pediatria
Volume27
Issue number2
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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