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1.
Int J Biol Macromol ; 156: 1022-1044, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32171830

RESUMO

Lanthanide nanoparticles and nanorods especially their biocompatible oxide forms like cerium oxide nanoparticles (CNPs) with therapeutic applications are used to cure neurological oxidative stresses. Thus it tempts to study their biocompatible aspects by interactions with several biologically significant molecules. In-Vitro interactions of 15-240 µM CNPs with water, Phosphate buffered saline (PBS), DMEM media, Insulin (Ins) hemoglobin (Hb) and ds-DNA at 37 °C were studied. Their physicochemical properties study by Borosil Mansingh Survismeter (BMS) showed the first order interaction with the protein-protein structure breaking behaviour of CNPs with Hb, Ins, and DNA. Zeta potential measurements of CNPs in different biological medium show a net increase in negative charge magnitude with good colloidal stability. Kb = 4 × 106 mM-1 of CNPs-DNA infer noncovalent interactions. Circular dichroism and FTIR revealed a loss of secondary conformation with increasing CNPs concentration. In-silico molecular docking depicts CNP interaction via conventional hydrogen bonding, carbon hydrogen bonding and electrostatic interactions at the minor groove of DNA. The study reports in-dept unfolding functional mechanism investigated by physicochemical, spectroscopic, and In-Silico approaches of protein on interactions with CNPs for safer-by-design use in medicine and pharmaceutics. Fundamentally the CeO2 in ~62% and Ce2O3 in ~38% with Ce4+ and Ce3+ oxidation potentials develop a unique case of electronic configurations with 4f05d06s0 and 4f15d06s0 electrons respectively which these studies a novel one.


Assuntos
Cério/química , Fenômenos Químicos , DNA/química , Hemoglobinas/química , Insulina/química , Nanopartículas Metálicas/química , Modelos Moleculares , Humanos , Modelos Teóricos , Conformação Molecular , Estrutura Molecular , Análise Espectral , Relação Estrutura-Atividade
2.
Drug Chem Toxicol ; 42(1): 1-8, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29281933

RESUMO

Magnetic iron oxide nanoparticles (IONs) display the ability to cross blood - brain barrier and are envisioned as diagnostic and therapeutic applications, but there are few studies on their potential embryonic toxicity in higher vertebrates. This study investigates interaction of IONs with egg albumen and its subsequent toxicity on chicken embryo. Physicochemical interactions of IONs with egg albumen revealed alterations in friccohesity and secondary structural changes due to weak Vander Waals forces. Toxicity assessment of IONs (10, 25, 50, 100, and 200 µg/ml doses) on chicken embryo accounted for 100% mortality at 200 µg/ml dose due to Fe2+ ions overload. However, lower doses (50 and 100 µg/ml) recorded decrement in whole weights and crown-rump lengths of chicken embryo possibly due to ION-albumen interactions. Histology of brain tissue revealed degeneration of neurons (50-60%) at 10-100 µg/ml dose range of IONs. Toxicity studies of IONs with diverse animal models are needed to set a toxicity benchmark for preventing embryonic toxicity prior to its use in biomedical applications. This is the first study on toxicity assessment of IONs in chicken embryo.


Assuntos
Encéfalo/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Nanopartículas de Magnetita/toxicidade , Neurônios/efeitos dos fármacos , Animais , Encéfalo/embriologia , Encéfalo/ultraestrutura , Embrião de Galinha , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Coração/embriologia , Fígado/efeitos dos fármacos , Fígado/embriologia , Fígado/ultraestrutura , Neurônios/ultraestrutura , Tamanho da Partícula , Baço/efeitos dos fármacos , Baço/embriologia , Baço/ultraestrutura
3.
Sci Rep ; 8(1): 4756, 2018 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-29555972

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are among abundantly used metal oxide NPs but their interactions with biomolecules and subsequent embryonic toxicity in higher vertebrates is not extensively reported. Physicochemical interactions of TiO2 NPs with egg albumen reveals that lower doses of TiO2 NPs (10 and 25 µg/ml) accounted for higher friccohesity and activation energy but an increment in molecular radii was recorded at higher doses (50 and 100 µg/ml). FTIR analysis revealed conformational changes in secondary structure of egg albumen as a result of electrostratic interactions between egg albumen and TiO2 NPs. The morphometric data of chicken embryo recorded a reduction at all the doses of TiO2 NPs, but toxicity and developmental deformity (omphalocele and flexed limbs) were recorded at lower doses only. Inductively coupled plasma optical emission spectrometry (ICP-OES) confirmed presence of Ti in chicken embryos. mRNA levels of genes involved in canonical and non-canonical Wnt signaling were lowered following TiO2 NPs treatment resulting in free radical mediated disruption of lateral plate mesoderm and somite myogenesis. Conformational changes in egg albumen and subsequent developmental deformity in chicken embryo following TiO2 NPs treatment warrants detailed studies of NP toxicity at lower doses prior to their biomedical applications.


Assuntos
Hérnia Umbilical/induzido quimicamente , Hérnia Umbilical/patologia , Nanopartículas , Titânio/química , Titânio/toxicidade , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Embrião de Galinha , Regulação da Expressão Gênica/efeitos dos fármacos , Tamanho da Partícula , Somitos/efeitos dos fármacos , Somitos/crescimento & desenvolvimento
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