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MgO nanoparticles coated with polyethylene glycol as carrier for 2-Methoxyestradiol anticancer drug.

ABSTRACT: Novel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer polyethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated 98.51 % of 2ME while liberation of 2ME was constant during 7 days at pH 2, 5 and 7.35. Finally, the MgO-PEG-2ME NPs decreased the viability of the prostate cancer cell line LNCap suggesting that this nanocomposite is suitable as a drug delivery system for anticancer prostate therapy.

SUBMITTER: Alfaro A

PROVIDER: S-EPMC6695098 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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MgO nanoparticles coated with polyethylene glycol as carrier for 2-Methoxyestradiol anticancer drug.

Alfaro Aline A León Andrea A Guajardo-Correa Emanuel E Reúquen Patricia P Torres Francisco F Mery Mario M Segura Rodrigo R Zapata Paula A PA Orihuela Pedro A PA

PloS one 20190815 8

Novel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer polyethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated ...[more]

PMID: 31415561

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Project description:Silver nanoparticles are widely used in various industrial and biomedical applications; however, little is known about their potential cardiotoxicity after pulmonary exposure, particularly in hypertensive subjects. We assessed the cardiotoxicity of polyethylene glycol (PEG)-coated AgNPs in hypertensive (HT) mice. Saline (control) or PEG-AgNPs (0.5 mg/kg) were intratracheally (i.t.) instilled four times (on days 7, 14, 21, and 28 post-angiotensin II or vehicle [saline] infusion). On day 29, various cardiovascular parameters were evaluated. Systolic blood pressure and heart rate were higher in PEG-AgNPs-treated HT mice than in saline-treated HT or PEG-AgNPs-treated normotensive mice. The heart histology of PEG-AgNPs-treated HT mice had comparatively larger cardiomyocyte damage with fibrosis and inflammatory cells when compared with saline-treated HT mice. Similarly, the relative heart weight and the activities of lactate dehydrogenase and creatine kinase-MB and the concentration of brain natriuretic peptide concentration were significantly augmented in heart homogenates of HT mice treated with PEG-AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG-AgNPs. Similarly, the concentrations of endothelin-1, P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in heart homogenates were significantly higher than in the other two groups when HT mice were exposed to PEG-AgNPs. Markers of inflammation and oxidative and nitrosative stress were significantly elevated in heart homogenates of HT mice given PEG-AgNPs compared with HT mice treated with saline or normotensive animals exposed to PEG-AgNPs. The hearts of HT mice exposed to PEG-AgNPs had significantly increased DNA damage than those of HT mice treated with saline or normotensive mice treated with AgNPs. In conclusion, the cardiac injury caused by PEG-AgNPs was aggravated in hypertensive mice. The cardiotoxicity of PEG-AgNPs in HT mice highlights the importance of an in-depth assessment of their toxicity before using them in clinical settings, particularly in patients with pre-existing cardiovascular diseases.

Project description:Background and aimA delivery system consisting of bone marrow mesenchymal stem cells (MSCs) loaded with polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (SPIONs) was constructed to treat a rat model of cisplatin (Cis)-induced nephrotoxicity with 1/10 of the common dose of anti-tumor necrosis factor-alpha (TNF-α) antibodies (infliximab).Materials and methodsMorphology, size, crystallinity, molecular structure, and magnetic properties of uncoated and PEG-coated SPIONs were analyzed. A delivery system consisting of MSCs containing infliximab-labeled PEG-coated SPIONs (Infliximab-PEG-SPIONs-MSCs) was generated and optimized before treatment. Fifty female Wistar rats were divided into five equal groups: Group 1: Untreated control; Group 2 (Cis): Rats were administered Cis through intraperitoneal (i.p.) injection (8 mg/kg) once a week for 4 weeks; Group 3 (Infliximab): Rats were injected once with infliximab (5 mg/kg), i.p. 3 days before Cis administration; Group 4 (Cis + MSCs): Rats were injected with Cis followed by an injection of 2 × 106 MSCs into the tail vein twice at a 1-week interval; and Group 5 (Cis + Infliximab (500 mg/kg)-PEG-SPIONs-MSCs): Rats were injected with the delivery system into the tail vein twice at a 1-week interval. Besides histological examination of the kidney, the Doppler ultrasound scanner was used to scan the kidney with the Gray-color-spectral mode.ResultsIn vivo, intra-renal iron uptake indicates the traffic of the delivery system from venous blood to renal tissues. Cis-induced nephrotoxicity resulted in a significant increase in TNF-α and malondialdehyde (MDA) (p < 0.05), bilirubin, creatinine, and uric acid (p < 0.01) levels compared with the untreated control group. The different treatments used in this study resulted in the amelioration of some renal parameters. However, TNF-α levels significantly decreased in Cis + Infliximab and Cis + MSCs (p < 0.05) groups. The serum levels of MDA significantly decreased in Cis + Infliximab (p < 0.05), Cis + MSCs (p < 0.05), and Cis + Infliximab-PEG-SPIONs-MSCs (p < 0.01). Furthermore, the serum activities of antioxidant enzymes were significantly elevated in the Cis + MSCs and Cis + Infliximab-PEG-SPIONs-MSCs groups (p < 0.05) compared to the Cis-induced nephrotoxicity rat model.ConclusionWith the support of the constructed MSCs-SPIONs infliximab delivery system, it will be possible to track and monitor cell homing after therapeutic application. This infliximab-loading system may help overcome some challenges regarding drug delivery to the target organ, optimize therapeutics' efficacy, and reduce the dose. The outcomes of the current study provide a better understanding of the potential of combining MSCs and antibodies-linked nanoparticles for the treatment of nephrotoxicity. However, further investigation is recommended using different types of other drugs. For new approaches development, we should evaluate whether existing toxicity analysis and risk evaluation strategies are reliable and enough for the variety and complexity of nanoparticles.

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MgO nanoparticles coated with polyethylene glycol as carrier for 2-Methoxyestradiol anticancer drug.

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MgO nanoparticles coated with polyethylene glycol as carrier for 2-Methoxyestradiol anticancer drug.

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