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1.
J Mater Chem B ; 7(12): 2081-2091, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-32254812

RESUMO

Clinically acceptable safety and efficacy are the most important issues for the design and synthesis of iron oxide MRI contrast agents. In order to meet the practical requirements, a kind of low molecular weight PAA-coated Fe3O4 nanoparticle (CS015) with super colloidal stability and low hypersensitivity benefitting from an ultrahigh carboxyl group density was developed in this study. The composition and physicochemical properties of the particles were characterized by TEM, XRD, FTIR and TGA. The ultrahigh density of COOH on the particles (33 COOH per nm2) was verified while a core size of 5.1 nm and a dynamic diameter of 41 nm with a narrow distribution were also achieved. The particles still showed excellent dispersity and stability even after a spray-drying or freeze-drying process, exposure to high temperature sterilized conditions and long-term storage. The nanoparticles could quickly capture iron ions in bulk solution which was confirmed by ITC results, and the bioactive iron concentration of CS015 was greatly decreased (0.54 ± 0.05 mg L-1) compared to that of commercially available ferumoxytol, iron sucrose and VSOP. Free iron ion release was 1120 times lower than the toxic concentration of iron. An excellent biocompatibility of CS015 with no obvious cytotoxicity and low risk of hypersensitivity has been manifested by cytotoxicity experiments and a passive cutaneous anaphylaxis test. The T1 and T2-weighted MRI contrast effects both in vitro and in vivo have also been verified which made CS015 a potential dual MRI contrast agent. Furthermore, theoretically calculated conformation was speculated and all the advantages mentioned above were benefited from the three dimensional brush-like texture of CS015. Therefore, these merits make the CS015 nanoplatform highly suitable in diagnostic applications as a MRI contrast agent.


Assuntos
Resinas Acrílicas , Meios de Contraste , Nanopartículas de Magnetita , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/administração & dosagem , Meios de Contraste/química , Estabilidade de Medicamentos , Humanos , Hipersensibilidade , Ferro/química , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/química , Anafilaxia Cutânea Passiva
2.
Biomaterials ; 222: 119442, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31491561

RESUMO

Polyelectrolyte modified iron oxide nanoparticles have great potential applications for clinical magnetic resonance imaging (MRI) and anemia treatments, however, possible associated heart toxicity is rarely reported. Here, polyacrylic acid (PAA)-coated Fe3O4 nanoparticles (PION) were synthesized and lethal reactions appeared when it was applied in vivo. The investigation of underlying mechanism showed that PION could break electrolyte balance and further resulted in serious heart failure, which was observed under color doppler ultrasound and dynamic vector blood flow technique. The results demonstrated that PION had a strong absorption tendency for divalent ions and the maximum tolerated dose (MTD) was lower than 100 mg/kg. From electrocardiography (ECG), PION presented an obvious impact on CaV1.2 ion channel, which leading to fatal arrhythmia. An appropriate solution for preventing this deadly effect was pre-chelation Ca2+ (n (Ca): n (COOH) = 3: 8) to PION (PION-Ca), which displayed much higher cardiac and electrophysiological safety when sealing the binding point of divalent cation ions with PAA. The injection in Beagle dogs further confirmed the safety of PION-Ca. This study explored the mechanism and offered a solution for cardiac toxicity induced by PAA-coated nanoparticles, which guides for enhancing the safety of such polyelectrolyte decorated nanoparticles and provides assurance for clinical applications.


Assuntos
Cardiotoxicidade/prevenção & controle , Imageamento por Ressonância Magnética/métodos , Resinas Acrílicas/química , Animais , Canais de Cálcio Tipo L/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cães , Eletrocardiografia , Compostos Férricos/química , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Nanopartículas/efeitos adversos , Nanopartículas/química , Ratos
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