Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles

Popescu, Roxana Cristina; Andronescu, Ecaterina; Vasile, Bogdan Ștefan; Trușcă, Roxana; Brăgaru, Adina; Mogoantă, Laurențiu; Mogoşanu, George Dan; Temelie, Mihaela; Radu, Mihai; Grumezescu, Alexandru Mihai; Savu, Diana

doi:10.3390/molecules22071080

Cited by 40 publications

(28 citation statements)

References 68 publications

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“…More importantly AuNPs-chemotherapeutic conjugate, in some cases, were more effective than chemotherapeutic alone. We compared the cytotoxicity of chemotherapeutics on cell lines used in this study (143B, PANC-1, MCF7) with literature data, and generally, we had similar results [31,32,41,42,[33][34][35][36][37][38][39][40]. For DOX, Kamba et al, reported that IC50 was around 0.5µg/mL (MG63, osteosarcoma cells), Yui et al, showed that IC 50 was approximately equal 2 µg/mL (PANC1 cells).…”

Section: Discussionsupporting

confidence: 65%

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics

Steckiewicz¹,

Barcińska²,

Sobczak³

et al. 2020

Int. J. Med. Sci.

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Due to the high toxicity of currently used chemotherapeutics, novel methods of cancer treatment are needed. Gold nanoparticles (AuNPs) seem to be an interesting alternative due to penetration through biological membranes and systemic barriers. AuNPs as carriers of chemotherapeutics allow for reduced concentrations whilst maintaining the expected effect, and thus reducing the costs of therapy and adverse effects. We synthesized AuNPs stabilized with reduced glutathione (GSH) and conjugated with doxorubicin (DOX), gemcitabine (GEM) or cytarabine (CTA). This is the first study in which cytarabine-AuNPs were synthesized and characterized. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), nuclear magnetic resonance spectroscopy (NMR) and highperformance liquid chromatography (HPLC) were used to chemically characterize obtained nanoparticles. Antitumor activity and safety of application were assessed by MTT assay in in vitro model (human osteosarcoma cells -143B, human osteoblast-hFOB1.19, breast cancer cells -MCF7, breast epithelial cells -MCF10A, pancreatic cancer cells -PANC-1, and pancreatic cells -hTERT-HPNE cells). We have shown that cellular response varies according to the type and concentration of AuNPs. At some concentrations, we were able to show selective cytotoxicity of our AuNPs conjugates only to cancer cell lines. Synthesized nanoparticles were more cytotoxic to tumor cell lines than chemotherapeutics alone.

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Section: Discussionsupporting

confidence: 65%

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics

Steckiewicz¹,

Barcińska²,

Sobczak³

et al. 2020

Int. J. Med. Sci.

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“…The bare iron oxide nanoparticles have been synthesized ( Supplementary Information, Section S1.1 ) using a modified chemical co-precipitation method, as in Popescu et al [ 18 ], which implied a 1.65:1 Fe 3+ :Fe 2+ ratio, in order to compensate the oxidation of Fe 2+ [ 20 , 21 ]. The biocompatibility of bare Fe 3 O 4 nanoparticles (NP) was proven by our in vitro data on cyto- and geno-toxicity ( Supplementary Information, Section S2.2 and Figure 2 H), confirming other reports [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…To test our hypothesis, mechanistic investigation concerning the effect of ionizing radiation on the internalization and cytotoxicity of NP-DOX have been performed in a MG-63 human osteosarcoma cell model. We synthesized the nanoparticles (as described in Popescu et al [ 18 ]) and then characterized them using relevant physico-chemical methods ( Supplementary Materials Sections S1.1 and S2.1 ). In vitro testing on MG-63 cells revealed information on the internalization, cyto- and geno-toxicity of NP-DOX and have been used to select the experimental conditions, concentrations and observation time points for the investigations we report here ( Supplementary Materials Section S2.2 ).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Internalization of Nanoparticles Following Ionizing Radiation Leads to Mitotic Catastrophe in MG-63 Human Osteosarcoma Cells

Popescu

Straticiuc

Mustăciosu

et al. 2020

IJMS

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This study aims to investigate whether ionizing radiation combined with doxorubicin-conjugated iron oxide nanoparticles (NP-DOX) improves the internalization and cytotoxic effects of the nano-carrier-mediated drug delivery in MG-63 human osteosarcoma cells. NP-DOX was designed and synthesized using the co-precipitation method. Highly stable and crystalline nanoparticles conjugated with DOX were internalized in MG-63 cells through macropinocytosis and located in the perinuclear area. Higher nanoparticles internalization in MG-63 cells previously exposed to 1 Gy X-rays was correlated with an early accumulation of cells in G2/M, starting at 12 h after treatment. After 48 h, the application of the combined treatment led to higher cytotoxic effects compared to the individual treatment, with a reduction in the metabolic capacity and unrepaired DNA breaks, whilst a low percent of arrested cells, contributing to the commitment of mitotic catastrophe. NP-DOX showed hemocompatibility and no systemic cytotoxicity, nor histopathological alteration of the main organs.

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“…The general side effects include bone marrow suppression, liver and kidney problems, nausea, fever, rash, shortness of breath and hair loss [31][32][33][34]. Therefore, for today, the possibility is actively studied to use GC in composition of magnetically sensitive NC and ML on their basis to create multi-functional antitumor medicines for targeted delivery and local therapy [35][36][37][38].…”

Section: Experimental Part and Discussionmentioning

confidence: 99%

Magnetically sensitive nanocomposites and magnetic liquids based on magnetite, gemcitabine, and antibody HER2

Petranovska¹,

Абрамов²,

Опанащук³

et al. 2019

Him. Fiz. Tehnol. Poverhni

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The processes of adsorption of gemcitabine (GC) on the surface of nanosized singledomain magnetite (Fe 3 O 4) have been investigated. Under the experiment conditions, the value of adsorption capacity A was ~ 37.2 mg/g, the extraction extent U = 33.13 %, the separation factor E = 82.58 mL/g. It has been determined that adsorption corresponds to the Freundlich model. The magnetic properties of nanocomposites (NС) Fe 3 O 4 @GC have been investigated. The average value of the thickness of the adsorbed layer of GC in the composition of Fe 3 O 4 @GC NC is 2.4±0.1 nm, as evaluated by the method of magnetic granulometry. Magnetic liquids (ML) have been synthesized based on magnetite and physiological solution (PS) stabilized with sodium oleate (Ol.Na) and polyethylene glycol (PEG), which contain GC and antibody (AB) HER2 (Fe 3 O 4 @GC/Ol.Na/PEG+PS). The properties of ML were investigated as well as cytotoxic/cytostatic activity with respect to HepG2 hepatocellular carcinoma of human liver. Parameters of ML based on magnetite were found: Fe 3 O 4 concentration-14 mg/mL, Fe 3 O 4 particle size-4-22 nm, average size of Fe 3 O 4 particles-10.8 nm; the average size of Fe 3 O 4 particles stabilized with sodium oleate-16.8 nm, saturation magnetization M ∞ = 14.1±2.5 % Gs, hypsometric height-25±10 % cm, viscosity η = 1.14±3 % mPa•s, density ρ ML = 1.14 ± 1.0 % g/cm 3 , the concentration of GC was 1.25 mg/mL, that of HER2 AB was 3.75 μg/mL. We have obtained the calculated and graphic data concerning the dependence of the surface area and the specific magnetization of saturation of Fe 3 O 4 @GC/Ol.Na/PEG on the thickness of GC layer, which can be useful for predicting of the nanoscale architecture of magnetically sensitive NC and ML in the manufacture of relative drugs. The synergistic nature of the influence of GC/Fe 3 O 4 /HER2 complex on HepG2 cells was revealed. It has been determined that IC50 for ML is 0.155 mg/mL, in the range of concentration of 0.025-0.1 mg/mL, ML is biocompatible with HepG2 cells. It has been shown that HER2 AB used alone in the investigated concentrations does not affect HepG2 cell viability/proliferation. In vitro, GC inhibits the proliferation of liver carcinoma cells, the IC50 value has been 0.002 mg/mL. The use of ML in complex with GC can increase the cytotoxic activity of the composite by 8-10 %. The ML+GC+HER2 AB complexes caused the synergistic effect and an increase in the cytotoxic activity, compared with GC used alone, up to 18-20 %, while GC contents reduced to 0.008 mg/mL. The results of the studies indicate that the use of ML based on magnetite, gemcitabine, and antibody increases the effectiveness of the antitumor medicines with a significant reduction in their dose and, respectively, the toxicoallergic reactions of the body, and nanosized magnetite can be promising for the manufacture of magnetically sensitive adsorption materials for medical purposes, e.g. for detoxification of an organism after GC therapy.

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Fabrication and Cytotoxicity of Gemcitabine-Functionalized Magnetite Nanoparticles

Cited by 40 publications

References 68 publications

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics

Assessment of Anti-Tumor potential and safety of application of Glutathione stabilized Gold Nanoparticles conjugated with Chemotherapeutics

Enhanced Internalization of Nanoparticles Following Ionizing Radiation Leads to Mitotic Catastrophe in MG-63 Human Osteosarcoma Cells

Magnetically sensitive nanocomposites and magnetic liquids based on magnetite, gemcitabine, and antibody HER2

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