Cytotoxicity of Methotrexate Conjugated to Glycerol Phosphate Modified Superparamagnetic Iron Oxide Nanoparticles

Autor(es)

Deda, Daiana K. ^[1] ; Cardoso, Roberta M. ^[1] ; Kawassaki, Rodrigo K. ^[1] ; de Oliveira, Andre R. ^[1] ; Toma, Sergio H. ^[1] ; Baptista, Mauricio S. ^[2] ; Araki, Koiti ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Fundamental Chem, Inst Chem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Nanoscience and Nanotechnology; v. 21, n. 3, p. 1451-1461, MAR 2021.
• Citações Web of Science: 0

Resumo

A systematic study was carried out to evaluate the uptake and cytotoxicity of methotrexate (MTX) conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) modified with glycerol phosphate (Glyc) and phosphorylethanolamine (PEA), using MCF-7 cancer cell line as model. The ligand shell composition was controlled in such a way to get SPIONs with nine different surface functionalization and up to three co-conjugated ligands but the very iron oxide core, in order to test and compare uptake and cytotoxicity, and verify possible additive effects. Folic acid (FA), the non-toxic analogue of MTX, was also explored as ligand for SPIONs. Glyc was shown to enhance dramatically the cellular uptake despite the high negative zeta potentials, whereas PEA, FA and MTX was found to have a much lower effect on the cellular uptake. Also, a significant ten times lowering of IC50 was observed for the co-conjugated MTX in the SPION-Glyc/PEA/MTX as compared to the free drug, whereas the analogue SPION-Glyc/PEA/FA nanoparticles exhibited no significant cytotoxicity. In short, the conjugation of MTX to SPIONs enhanced dramatically its cytotoxicity and decreased the IC50 value against MCF-7 tumor cells as compared to the free drug, probably due to the enhanced uptake of SPIONs as a result of their surface modification with Glyc/PEA, demonstrating that SPION-Glyc/PEA is a good nanocarrier for co-conjugated methotrexate. (AU)

• Processo FAPESP: 18/21489-1 - Nanotecnologia supramolecular: design, materiais e dispositivos
• Beneficiário: Henrique Eisi Toma
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/02151-2 - Desenvolvimento de nanoagente teranóstico bimodal para MRI e PET/SPECT
• Beneficiário: Rodrigo Ken Kawassaki
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto