Browsing by Author "Fernandez, FB"

Now showing 1 - 12 of 12
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    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, PRH
    Despite 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.
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    Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fbrosis using pullulan stabilized multi-functional iron oxide nanoprobe
    (Scientific Reports., 2021-09) Saraswathy, A; Nazeer, SS; Nimi, N; Hema, S; Parvathy, RS; Jibin, K; Victor, M; Fernandez, FB; Sabareeswaran, A; Shenoy, SJ; Harikrishna Varma, PR; Jayasre, RS
    Early diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes. In this work, a systematic study is reported to develop a dual function and biocompatible nanoprobe for liver specific diagnostic and therapeutic applications. A polysaccharide polymer, pullulan stabilized iron oxide nanoparticle (P-SPIONs) enabled high liver specificity via asialogycoprotein receptor mediation. Longitudinal and transverse magnetic relaxation rates of 2.15 and 146.91 mM−1 s−1 respectively and a size of 12 nm, confirmed the T2 weighted magnetic resonance imaging (MRI) efficacy of P-SPIONs. A current of 400A on 5 mg/ml of P-SPIONs raised the temperature above 50 °C, to facilitate effective hyperthermia. Finally, a NIR dye conjugation facilitated targeted dual imaging in liver fibrosis models, in vivo, with favourable histopathological results and recommends its use in early stage diagnosis using MRI and optical imaging, and subsequent therapy using hyperthermia.
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    Cyclic RGD Peptide Conjugated Trypsin Etched Gold Quantum Clusters: Novel Biolabeling Agents for Stem Cell Imaging
    (Journal of Stem Cells., 2012) Das, B; Fernandez, FB; John, A; Sharma, CP
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    Effective cellular internalization of silica-coated CdSe quantum dots for high contrast cancer imaging and labeling applications.
    (Cancer Nanotechnology., 2015-01) Vibin, M; Vinayakan, R; John, A; Fernandez, FB; Abraham, A
    The possibility of developing novel contrast imaging agents for cancer cellular labelling and fluorescence imaging applications were explored using silica-coated cadmium selenide (CdSe) quantum dots (QDs). The time dependent cellular internalization efficiency study was carried out using Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) and Confocal Laser Scanning Microscopy (cLSM) after exposing QDs to stem cells and cancer cells. The strong fluorescence from the cytoplasm confirmed that the QDs were efficiently internalized by the cells. The internalization maxima were observed at the fourth hour of incubation in both stem and cancer cells. Further, the in vitro fluorescence imaging as well as localization study of QDs were performed in various cells. Moreover, high contrast in vivo tumor imaging efficiency of silica-coated CdSe QDs was performed in ultrathin sections of tumor mice, and the results confirmed its effective role in cellular imaging and labelling in cancer and other diseases.
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    Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Management of COVID19-Associated Lung Injury: A Review on Publications, Clinical Trials and Patent Landscape
    (. Tissue Engineering and Regenerative Medicine, 2022-08) Anand, Krishnan; Muthusamy, S; Fernandez, FB; Kasoju, N
    The unprecedented COVID-19 pandemic situation forced the scientific community to explore all the possibilities from various fields, and so far we have seen a lot of surprises, eureka moments and disappointments. One of the approaches from the cellular therapists was exploiting the immunomodulatory and regenerative potential of mesenchymal stromal cells (MSCs), more so of MSC-derived extracellular vesicles (EVs)-particularly exosomes, in order to alleviate the cytokine storm and regenerate the damaged lung tissues. Unlike MSCs, the EVs are easier to store, deliver, and are previously shown to be as effective as MSCs, yet less immunogenic. These features attracted the attention of many and thus led to a tremendous increase in publications, clinical trials and patent applications. This review presents the current landscape of the field and highlights some interesting findings on MSC-derived EVs in the context of COVID-19, including in silico, in vitro, in vivo and case reports. The data strongly suggests the potential of MSC-derived EVs as a therapeutic regime for the management of acute lung injury and associated complications in COVID-19 and beyond.
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    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, PRH
    Ferrofluid-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.
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    Preparation of hydroxyapatite porous scaffolds from a coral like synthetic inorganic precusrsor for use as a bone graft substitute and a drug delivery vehicle
    (Materials Science and Engineering C, 2018-11) Nimi, N; Palangadan, R; Fernandez, FB; Varma, H
    A novel surfactant free hydrothermal method was developed for the preparation of large hydroxyapatite scaffolds. Synthetic calcium carbonate (calcite) was used as the starting material which when mixed with an inorganic setting solution containing phosphoric acid and sodium hydroxide forms the porous precursor body with pore size 20-700 μm. The porous precursor body was then hydrothermally converted to hydroxyapatite scaffolds when treated in basic phosphate solution of pH 10.5 at 150 °C and 15 bar pressure maintaining the structural stability and integrity. X-ray diffraction and the Fourier transform infrared spectroscopy confirmed that the developed material consist of single phase crystalline hydroxyapatite. Surface morphology and microstructures were studied using scanning electron microscopy and porosity was evaluated by micro CT analysis. The cell material interactions evaluated by cell viability assays and live cell staining methods confirmed the cell compatibility. The drug release study at physiological pH implied that the developed materials could be promising in sustained long-term release. The results emerged have shown that the hydrothermal conversion of inorganic coral-like precursor is effective to produce porous bioactive hydroxyapatite scaffolds for bone regeneration as well as drug delivery vehicles for the treatment of infectious bone diseases such as osteomyelitis.
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    Pulsed laser deposition and in vitro characteristics of triphasic - HASi composition on titanium
    (JOURNAL OF BIOMATERIALS APPLICATIONS, 2014) Palangadan, R; Sukumaran, A; Fernandez, FB; John, A; Varma, H
    Pulsed laser deposition was used to deposit bioactive triphasic glass-ceramic composition (HASi) over titanium substrate using dense HASi target. Bioactive glass compositions are considered the most useful synthetic materials for immediate bone attachment because of its bioresorption, osteoconduction and osteointegration characteristics under invivo conditions. The disadvantage of its brittleness associated with bioactive glass-ceramics has prompted its coating over metallic implants for the combination of duo mechanical and bioactive properties. The hard HASi target was able to undergo laser ablation under ambient gas pressure without bulk erosion of the target. Laser deposition was found to be efficient in depositing triphasic composition for immediate bone integration. The target and deposits were analyzed for the phase, composition and microstructural characteristics by means of X-ray diffraction, Fourier transform infrared spectroscopy, energy-dispersive X-ray analysis and scanning electron microscopy. Simultaneously, the adherent nature and mechanical behaviour of deposits were confirmed by scratch test and micro-indentation methods. Further, the invitro dissolution and bioactivity were assessed by soaking in simulated body fluid followed by elemental analysis using inductively coupled plasma spectroscopy. The deposits were found to be cell-friendly, which was indicated by the phenomenology of stem cells under invitro conditions.
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    Pulsed laser deposition and in vitro characteristics of triphasic ? HASi composition on titanium
    (Journal of Biomaterials Applications., 2014-02) Palangadan, R; Sukumaran, A; Fernandez, FB; John, A; Varma, H
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    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, HK
    Increasing 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.
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    Short-term studies using ceramic scaffolds in lapine model for osteochondral defect amelioration
    (BIOMEDICAL MATERIALS, 2012) Fernandez, FB; Shenoy, S; Babu, SS; Varma, HK; John, A
    This study was undertaken to glean preliminary information on the role of triphasic ceramic coated hydroxyapatite (HASi) and biphasic (alpha-tricalcium phosphate and hydroxyapatite based) calcium phosphate (BCP) for the development of osteochondral constructs. The proposed constructs were tested for performance in vitro with rabbit adipose-derived mesenchymal stem cells (RADMSCs) and further analysed in vivo in a lapine model for osteochondral defect amelioration. Desirable scaffolding architecture ensuring favourable conditions for cell attachment, nutrient exchange and neo-tissue organization was achieved by the synthesis of porous ceramic blocks and characterizations were carried out using x-ray diffraction and Fourier transform infrared spectroscopy. The cytocompatibility of the scaffold-cell combination product was evaluated using microscopy techniques that proved the scaffold to be non-cytotoxic and favourable for cell growth and proliferation. Short-term implantation studies were conducted with bare cylindrical HASi and BCP scaffolds, press fit deep into the bony bed of the median femoral condyles of the rabbit, which resulted in favourable specific in vivo response of de novo cartilage-like cells on the surface and sub-surface bony trabeculae. The generated pilot data will help to assess the severity of proposed procedures before embarking on scaled-up efforts.
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    Synthesis, Characterization and Bio-Labeling Studies of Trypsin Stabilized Silver Quantum Clusters
    (Journal of Biomaterials and Tissue Engineering., 2012) Das, B; Fernandez, FB; John, A; Sharma, CP