Dataset Information

Synthesis and Anti-Melanoma Activity of L-Cysteine-Coated Iron Oxide Nanoparticles Loaded with Doxorubicin.

ABSTRACT: In this study, we report on the synthesis of L-Cysteine (L-Cys)-coated magnetic iron oxide nanoparticles (NPs) loaded with doxorubicin (Dox). The Fe₃O₄-L-Cys-Dox NPs were extensively characterized for their compositional and morpho-structural features using EDS, SAED, XRD, FTIR and TEM. XPS, Mӧssbauer spectroscopy and SQUID measurements were also performed to determine the electronic and magnetic properties of the Fe₃O₄-L-Cys-Dox nanoparticles. Moreover, by means of a FO-SPR sensor, we evidenced and confirmed the binding of Dox to L-Cys. Biological tests on mouse (B16F10) and human (A375) metastatic melanoma cells evidenced the internalization of magnetic nanoparticles delivering Dox. Half maximum inhibitory concentration IC50 values of Fe₃O₄-L-Cys-Dox were determined for both cell lines: 4.26 µg/mL for A375 and 2.74 µg/mL for B16F10, as compared to 60.74 and 98.75 µg/mL, respectively, for unloaded controls. Incubation of cells with Fe₃O₄-L-Cys-Dox modulated MAPK signaling pathway activity 3 h post-treatment and produced cell cycle arrest and increased apoptosis by 48 h. We show that within the first 2 h of incubation in physiological (pH = 7.4) media, ~10-15 µM Dox/h was released from a 200 µg/mL Fe₃O₄-L-Cys-Dox solution, as compared to double upon incubation in citrate solution (pH = 3), which resembles acidic environment conditions. Our results highlight the potential of Fe₃O₄-L-Cys-Dox NPs as efficient drug delivery vehicles in melanoma therapy.

SUBMITTER: Toderascu LI

PROVIDER: S-EPMC9966685 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Synthesis and Anti-Melanoma Activity of L-Cysteine-Coated Iron Oxide Nanoparticles Loaded with Doxorubicin.

Toderascu Luiza Izabela LI Sima Livia Elena LE Orobeti Stefana S Florian Paula Ecaterina PE Icriverzi Madalina M Maraloiu Valentin-Adrian VA Comanescu Cezar C Iacob Nicusor N Kuncser Victor V Antohe Iulia I Popescu-Pelin Gianina G Stanciu George G Ionita Petre P Mihailescu Cristian N CN Socol Gabriel G

Nanomaterials (Basel, Switzerland) 20230204 4

In this study, we report on the synthesis of L-Cysteine (L-Cys)-coated magnetic iron oxide nanoparticles (NPs) loaded with doxorubicin (Dox). The Fe3O4-L-Cys-Dox NPs were extensively characterized for their compositional and morpho-structural features using EDS, SAED, XRD, FTIR and TEM. XPS, Mӧssbauer spectroscopy and SQUID measurements were also performed to determine the electronic and magnetic properties of the Fe3O4-L-Cys-Dox nanoparticles. Moreove ...[more]

PMID: 36838989

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Project description:Although doxorubicin (DOX) is an effective anti-cancer drug with cytotoxicity in a variety of different tumors, its effectiveness in treating glioblastoma multiforme (GBM) is constrained by insufficient penetration across the blood-brain barrier (BBB). In this study, biocompatible magnetic iron oxide nanoparticles (IONPs) stabilized with trimethoxysilylpropyl-ethylenediamine triacetic acid (EDT) were developed as a carrier of DOX for GBM chemotherapy. The DOX-loaded EDT-IONPs (DOX-EDT-IONPs) released DOX within 4 days with the capability of an accelerated release in acidic microenvironments. The DOX-loaded EDT-IONPs (DOX-EDT-IONPs) demonstrated an efficient uptake in mouse brain-derived microvessel endothelial, bEnd.3, Madin-Darby canine kidney transfected with multi-drug resistant protein 1 (MDCK-MDR1), and human U251 GBM cells. The DOX-EDT-IONPs could augment DOX's uptake in U251 cells by 2.8-fold and significantly inhibited U251 cell proliferation. Moreover, the DOX-EDT-IONPs were found to be effective in apoptotic-induced GBM cell death (over 90%) within 48 h of treatment. Gene expression studies revealed a significant downregulation of TOP II and Ku70, crucial enzymes for DNA repair and replication, as well as MiR-155 oncogene, concomitant with an upregulation of caspase 3 and tumor suppressors i.e., p53, MEG3 and GAS5, in U251 cells upon treatment with DOX-EDT-IONPs. An in vitro MDCK-MDR1-GBM co-culture model was used to assess the BBB permeability and anti-tumor activity of the DOX-EDT-IONPs and DOX treatments. While DOX-EDT-IONP showed improved permeability of DOX across MDCK-MDR1 monolayers compared to DOX alone, cytotoxicity in U251 cells was similar in both treatment groups. Using a cadherin binding peptide (ADTC5) to transiently open tight junctions, in combination with an external magnetic field, significantly enhanced both DOX-EDT-IONP permeability and cytotoxicity in the MDCK-MDR1-GBM co-culture model. Therefore, the combination of magnetic enhanced convective diffusion and the cadherin binding peptide for transiently opening the BBB tight junctions are expected to enhance the efficacy of GBM chemotherapy using the DOX-EDT-IONPs. In general, the developed approach enables the chemotherapeutic to overcome both BBB and multidrug resistance (MDR) glioma cells while providing site-specific magnetic targeting.

Dataset Information

Synthesis and Anti-Melanoma Activity of L-Cysteine-Coated Iron Oxide Nanoparticles Loaded with Doxorubicin.

Publications

Synthesis and Anti-Melanoma Activity of L-Cysteine-Coated Iron Oxide Nanoparticles Loaded with Doxorubicin.

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