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

2021 ◽  
Vol 21 (3) ◽  
pp. 1451-1461
Author(s):  
Daiana K. Deda ◽  
Roberta M. Cardoso ◽  
Rodrigo K. Kawassaki ◽  
André R. de Oliveira ◽  
Sergio H. Toma ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Cellular Uptake ◽  
Cancer Cell Line ◽  
Superparamagnetic Iron Oxide ◽  
Free Drug ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Glycerol Phosphate ◽  
Mcf 7

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.

TARGETING CYCLIN B1 WITH ANTISENSE OLIGONUCLETOTIDES- COATED SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES

2018 ◽  
Vol 6 (10) ◽  
Author(s):  
Hosam Zaghloul ◽  
Doaa A. Shahin ◽  
Ibrahim El- Dosoky ◽  
Mahmoud E. El-awady ◽  
Fardous F. El-Senduny ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Cellular Uptake ◽  
Superparamagnetic Iron Oxide ◽  
Cyclin B1 ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles ◽  
Mcf7 Cells ◽  
M Phase ◽  
The Impact

Antisense oligonucleotides (ASO) represent an attractive trend as specific targeting molecules but sustain poor cellular uptake meanwhile superparamagnetic iron oxide nanoparticles (SPIONs) offer stability of ASO and improved cellular uptake. In the present work we aimed to functionalize SPIONs with ASO targeting the mRNA of Cyclin B1 which represents a potential cancer target and to explore its anticancer activity. For that purpose, four different SPIONs-ASO conjugates, S-M (1–4), were designated depending on the sequence of ASO and constructed by crosslinking carboxylated SPIONs to amino labeled ASO. The impact of S-M (1–4) on the level of Cyclin B1, cell cycle, ROS and viability of the cells were assessed by flowcytometry. The results showed that S-M3 and S-M4 reduced the level of Cyclin B1 by 35 and 36%, respectively. As a consequence to downregulation of Cyclin B1, MCF7 cells were shown to be arrested at G2/M phase (60.7%). S-M (1–4) led to the induction of ROS formation in comparison to the untreated control cells. Furthermore, S-M (1–4) resulted in an increase in dead cells compared to the untreated cells and SPIONs-treated cells. In conclusion, targeting Cyclin B1 with ASO-coated SPIONs may represent a specific biocompatible anticancer strategy.

How a grafting anchor tailors the cellular uptake and in vivo fate of dendronized iron oxide nanoparticles

2017 ◽  
Vol 5 (26) ◽  
pp. 5152-5164 ◽  
Author(s):  
C. Bordeianu ◽  
A. Parat ◽  
C. Affolter-Zbaraszczuk ◽  
R. N. Muller ◽  
S. Boutry ◽  
...  
Keyword(s):  
Thermal Decomposition ◽  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Cellular Uptake ◽  
Focal Point ◽  
Superparamagnetic Iron Oxide ◽  
Superparamagnetic Iron Oxide Nanoparticles ◽  
Oxide Nanoparticles

Superparamagnetic iron oxide nanoparticles synthesized by thermal decomposition have been grafted with two dendrons bearing respectively a monophosphonic anchor (D2) or a biphosphonic tweezer (D2-2P) at their focal point.

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