Original scientific paper

https://doi.org/10.5562/cca3997

Facile Design of Superparamagnetic Core-Shell EDC-Ascorbate-Fe3O4 Nanocomposites for Targeted Delivery of Doxorubicin to Triple Negative Breast Tumor by Fenton Reaction

S. H. Mirjalili ; Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran
Mohammad Reza Nateghi ; Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran
F. Kalantari-Fotooh ; Department of Chemistry, Yazd Branch, Islamic Azad University, Yazd, Iran

Abstract

Triple negative breast cancer (TNBC) phenotype accounts for its significant resistance to chemotherapy and other therapeutic procedures. So, the establishment of better and effective therapeutic procedures has become a challenge during recent years. Doxorubicin is a potent chemotherapeutic candidate but its prominent side effects can be subsided via its combination with nanocarriers. So, the present study was aimed to design ascorbic acid modified biopolymeric EDC/NHS-modified magnetic nanoparticles (MNP@MNP@AA-EDC/NHS-DOX for doxorubicin drug delivery to the triple negative breast cancers cell lines of MDA-MB-231, MDA-MB-468 and HCC1937. Monodisperse Fe3O4 MNPs were prepared by chemical co-precipitation method. According to the SEM and DLS results, MNP@AA-EDC/NHS-DOX, MNPs@AA, MNP@AA-MNP@AA-EDC/NHS and MNP@AA-EDC/NHS-DOX had average particle diameter of 53, 79 and 95 nm, respectively. While, XRD analysis showed that the MNP material had the strongest Fe crystal peak, while surface modified MNP@AA-EDC/NHS-DOX did not alter the characteristic properties of MNPs. VSM magnetization analysis revealed that MNP@AA-EDC/NHS-DOX exhibited sufficient paramagnetic potential in the presence of external magnetic field. The TG analysis showed that thermal decomposition capacity of present nanocomposites was: MNPs > MNP@AA-EDC/NHS > AA-MNPs > MNP@AA-EDC/NHS-DOX. AA-modified MNPs did not completely lose their thermal stability as compared to other modifications. Alamar blue analysis revealed that the bare MNPs did have non-significant cytotoxicity in MDA-MB-231, MDA-MB-468 and HCC1937 cell lines (p > 0.001). While, MNP@AA-EDC/NHS-DOX at 0.1, 1.0 and 10 μg/mL DOX concentrations showed significantly lowered cell survival percentages as compared to the free DOX regimens after 24 and 72h. While, HCC1937 cell line had the most accumulation of free (1.42 > 0.93 > 0.9 pg DOX/cell) and conjugated DOX (2.64 > 2.2 > 1.91 pg DOX/cell) after 6 h of incubation period as compared to MDA-MB-468 and MDA-MB-231, respectively (* p < 0.05). Present results provide a new insight into the design of paramagnetic targeted drug delivery nanocomposite system to overcome the obstacles and side effects of conventional chemotherapeutic agents.

Keywords

triple negative breast cancer; ascorbic acid modified MNPs; ferromagnetism; doxorubicin; Fenton reaction

Hrčak ID:

313325

URI

https://hrcak.srce.hr/313325

Publication date:

10.12.2023.

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