Browsing by Author "Beeran, AE"
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Item An aqueous method for the controlled manganese (Mn2+) substitution in superparamagnetic iron oxide nanoparticles for contrast enhancement in MRI(PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 2015) Beeran, AE; Nazeer, SS; Fernandez, FB; Muvvala, KS; Wunderlich, W; Anil, S; Vellappally, S; Rao, MSR; John, A; Jayasree, RS; Varma, PRHDespite the success in the use of superparamagnetic iron oxide nanoparticles (SPION) for various scientific applications, its potential in biomedical fields has not been exploited to its full potential. In this context, an in situ substitution of Mn2+ was performed in SPION and a series of ferrite particles, MnxFe1-xFe2O4 with a varying molar ratio of Mn2+ : Fe2+ where 'x' varies from 0-0.75. The ferrite particles obtained were further studied in MRI contrast applications and showed appreciable enhancement in their MRI contrast properties. Manganese substituted ferrite nanocrystals (MnIOs) were synthesized using a novel, one-step aqueous co-precipitation method based on the use of a combination of sodium hydroxide and trisodium citrate (TSC). This approach yielded the formation of highly crystalline, superparamagnetic MnIOs with good control over their size and bivalent Mn ion crystal substitution. The presence of a TSC hydrophilic layer on the surface facilitated easy dispersion of the materials in an aqueous media. Primary characterizations such as structural, chemical and magnetic properties demonstrated the successful formation of manganese substituted ferrite. More significantly, the MRI relaxivity of the MnIOs improved fourfold when compared to SPION crystals imparting high potential for use as an MRI contrast agent. Further, the cytocompatibility and blood compatibility evaluations demonstrated excellent cell morphological integrity even at high concentrations of nanoparticles supporting the non-toxic nature of nanoparticles. These results open new horizons for the design of biocompatible water dispersible ferrite nanoparticles with good relaxivity properties via a versatile and easily scalable co-precipitation route.Item Multifunctional nano manganese ferrite ferrofluid for efficient theranostic application(Colloids and Surfaces B: Biointerfaces., 2015-11) Beeran, AE; Fernandez, FB; Nazeer, SS; Jayasree, RS; John, A; Anil, S; Vellappally, S; Al Kheraif, AAA; Varma, PRHFerrofluid-based manganese (Mn2+) substituted superparamagnetic iron oxide nanoparticles stabilized by surface coating with trisodium citrate (MnIOTCs) were synthesized for enhanced hyperthermic activity and use as negative magnetic resonance imaging (MRI) contrast media intended for applications in theranostics. The synthesized MnIOTC materials were characterized based on their physicochemical and biological features. The crystal size and the particle size at the nano level were studied using XRD and TEM. The presence of citrate molecules on the crystal surface of the iron oxide was established by FTIR, TGA, DLS and zeta potential measurements. The superparamagnetic property of MnIOTCs was measured using a vibrating sample magnetometer. Superparamagnetic iron oxide substituted with Mn2+ with a 3:1 molar concentration of Mn2+ to Fe2+ and surface modified with trisodium citrate (MnIO75TC) that exhibited a high T2 relaxivity of 184.6 mM−1 s−1 and showed excellent signal intensity variation in vitro. Hyperthermia via application of an alternating magnetic field to MnIO75TC in a HeLa cell population induced apoptosis, which was further confirmed by FACS and cLSM observations. The morphological features of the cells were highly disrupted after the hyperthermia experiment, as evidenced from E-SEM images. Biocompatibility evaluation was performed using an alamar blue assay and hemolysis studies, and the results indicated good cytocompatibility and hemocompatibility for the synthesized particles. In the current study, the potential of MnIO75TC as a negative MRI contrast agent and a hyperthermia agent was demonstrated to confirm its utility in the burgeoning field of theranostics.Item Self-assembled superparamagnetic nanocomposite-labelled cells for noninvasive, controlled, targeted delivery and therapy(RSC Advances, 2015-04) Beeran, AE; Francis Fernandez, FB; John, A; Harikrishna, PREfficient delivery of cells to targeted sites at optimal concentrations within rational limits of damage to normal tissue is a major challenge for cell delivery. With the help of magnetic nanoparticles binding to the surface of cells, it is possible to manipulate and control cell mobility using an external magnetic field. Here, we demonstrate physical entrapment of magnetic nanocomposites onto cell surfaces and their manipulation by an external magnetic field. Uniformly embedded nano iron oxide particles in a hydroxyapatite crystallite (HAIO) were synthesized via co-precipitation method. Physiochemical and biological evaluation of the above nanocomposite system showed that the HAIO containing 50 wt% iron oxide (HAIO50) possessed excellent magnetic properties and good cytocompatibility. Prussian blue staining and flow cytometric evaluation of cell–material interactions indicated uniform uptake and a dose-dependent interaction. HAIO50 is found to be a novel matrix for use as an effective and cytocompatible avenue for cell separation, evidenced via Coulter analysis as well as fluorescent imaging of live cells. Post-magnetic separation analysis of cell viability via confocal laser scanning microscopy (CLSM) showed the normal structure and proliferation of separated cells. HAIO50 may be used as an efficient matrix for magnetic non-invasive manipulation and for further cell delivery applicationsItem Self-Controlled Hyperthermia & MRI Contrast Enhancement via Iron Oxide Embedded Hydroxyapatite Superparamagnetic particles for Theranostic Application(ACS Biomaterials Science & Engineering, 2019-05) Beeran, AE; Fernandez, FB; Varma, HKIncreasing effectiveness of cancer therapeutics requires a multipronged approach. Delivery of controlled hyperthermia in the ranges of 43 to 45 °C on site aided by superparamagnetic particles ensures cell death via the apoptosis pathway.We demonstrated the use of iron-oxide embedded hydroxyapatite (HAIO) superparamagnetic particles for delivery of controlled hyperthermia and contrast enhancement in MRI. To determine optimal hyperthermia delivery, we used 5 and 10 mg/mL concentrations of HAIO on various magnetic fields in alternating magnetic field (AMF) study. Time–temperature profile and specific loss power (SLP) data revealed that HAIO delivered precisely controlled temperature in contrast to superparamagnetic iron oxide nanoparticles (SPIONs). Earlier studies had demonstrated that HAIO concentrations of 0.5 to 3 mg/mL are cytocompatible. Exposure of HeLa cells to HAIO at a concentration of 2 mg/mL and applied field of 33.8 mT for a period of 30 min resulted in apoptosis induction in 75% of population. Significant cellular disruption was affirmed via FACS, ESEM and cLSM techniques. An aqueous phantom study and in vitro cell culture study evaluation indicated relaxivity of 50.92 mM–1 s–1 and good pixel intensity variation in MRI. The current study assesses the potential of HAIO to deliver controlled hyperthermia and act as a negative MRI contrast agent. Repeated experiments have confirmed enhanced utility of the technique in the burgeoning field of theranostics.