RESUMEN
Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON(LA-BSA), which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON(LA-BSA) particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON(LA-BSA) changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment.
Asunto(s)
Ácidos Láuricos/química , Nanopartículas de Magnetita/química , Albúmina Sérica Bovina/química , Ultrafiltración/métodos , Animales , Bovinos , Coloides/química , Coloides/aislamiento & purificación , Humanos , Hipertermia Inducida , Células Jurkat , Ácidos Láuricos/aislamiento & purificación , Magnetismo , Albúmina Sérica Bovina/aislamiento & purificación , Propiedades de SuperficieRESUMEN
OBJECTIVE: The aim of the present study is to present the results of in vitro experiments with possible relevance in the treatment of Alzheimer's disease (AD). BACKGROUND DATA: Despite intensive research efforts, there is no treatment for AD. One root cause of AD is the extra- and intracellular deposition of amyloid-beta (Aß) fibrils in the brain. Recently, it was shown that extracellular Aß can enter brain cells, resulting in neurotoxicity. METHODS: After internalization of Aß(42) into human neuroblastoma (SH-EP) cells, they were irradiated with moderately intense 670-nm laser light (1000 Wm(-2)) and/or treated with epigallocatechin gallate (EGCG). RESULTS: In irradiated cells, Aß(42) aggregate amounts were significantly lower than in nonirradiated cells. Likewise, in EGCG-treated cells, Aß(42) aggregate amounts were significantly lower than in non-EGCG-treated cells. Except for the cells simultaneously laden with Aß(42) and EGCG, there was a significant increase in cell numbers in response to laser irradiation. EGCG alone had no effect on cell proliferation. Laser irradiation significantly increased ATP levels in Aß(42)-free cells, when compared to nonirradiated cells. Laser-induced clearance of Aß(42) aggregates occurred at the expense of cellular ATP. CONCLUSIONS: Irradiation with moderate levels of 670-nm light and EGCG supplementation complementarily reduces Aß aggregates in SH-EP cells. Transcranial penetration of moderate levels of red to near-infrared (NIR) light has already been amply exploited in the treatment of patients with acute stroke; the blood-brain barrier (BBB) penetration of EGCG has been demonstrated in animals. We hope that our approach will inspire a practical therapy for AD.