Asialoglycoprotein receptor targeted optical and magnetic resonance imaging and therapy of liver fibrosis using pullulan stabilized multi-functional iron oxide nanoprobe.

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.

Utility of Chitra-HASi Granules in Cystic Defects of the Maxillofacial Region: A Pilot Study.

BACKGROUND: Cystic defects that are critical sized or larger require bone replacement strategies. However, due to inherent disadvantages of the various types of grafts, none of the available materials are best suited for these defects. Among the alloplastic materials, hydroxyapatite (HA)-based grafts are the most popular, due to their osteoconductive nature and resemblance to mineral bone. The aim of the study was to assess the utility of the novel material "Chitra-HASi" as a bone substitute in the maxillofacial region. MATERIALS AND METHODS: In a single-arm, prospective study, patients with radicular and dentigerous cysts were included and the minimum defect size was standardized at 20 × 20 mm or above. The Chitra-HASi material was developed by a wet precipitation technique and adopted for use following multiple in vitro and in vivo studies, confirming its safety and biocompatibility profile. All cysts underwent enucleation, followed by peripheral ostectomy and apicectomy of the teeth involved. The HASi graft was packed inside the cystic defect in a granular form and covered with a mucoperiosteal flap. Panoramic radiographs were taken preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: Twenty-three patients were included in the study, of which only 10 patients could be followed up for 12 months after graft placement. The mean preoperative bone density was found to be 14.9% ± 4.97 (standard deviation), whereas the postoperative 3-month, 6-month, and 12-month densities had a mean difference of -11.3%, -22.9%, and -37.3%, respectively, and the differences were statistically significant. Minor complications such as sinus formation (n = 7) and extrusion of granules (n = 4) were noted, which were managed conservatively. Only two patients required graft removal secondary to infection, leading to a persistent sinus tract. CONCLUSION: The results of the study suggest that Chitra-HASi granules show potential as an alternative to other bone substitutes. The addition of silica to the porous HA material offers superior strength characteristics and needs long-term evaluation to assess its stability in large cystic defects.

Self-Controlled Hyperthermia & MRI Contrast Enhancement via Iron Oxide Embedded Hydroxyapatite Superparamagnetic particles for Theranostic Application.

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.

Multifunctional nano manganese ferrite ferrofluid for efficient theranostic application.

Ferrofluid-based manganese (Mn(2+)) 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 Mn(2+) with a 3:1 molar concentration of Mn(2+) to Fe(2+) and surface modified with trisodium citrate (MnIO75TC) that exhibited a high T2 relaxivity of 184.6mM(-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.

An aqueous method for the controlled manganese (Mn(2+)) substitution in superparamagnetic iron oxide nanoparticles for contrast enhancement in MRI.

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 Mn(2+) was performed in SPION and a series of ferrite particles, MnxFe1-xFe2O4 with a varying molar ratio of Mn(2+) : Fe(2+) 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.

Effective cellular internalization of silica-coated CdSe quantum dots for high contrast cancer imaging and labelling applications.

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.