Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM-1 s-1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.

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.

Fluorescent nanonetworks: a novel bioalley for collagen scaffolds and tissue engineering.

Native collagen is arranged in bundles of aligned fibrils to withstand in vivo mechanical loads. Reproducing such a process under in vitro conditions has not met with major success. Our approach has been to induce nanolinks, during the self-assembly process, leading to delayed rather than inhibited fibrillogenesis. For this, a designed synthesis of nanoparticles - using starch as a template and a reflux process, which would provide a highly anisotropic (star shaped) nanoparticle, with large surface area was adopted. Anisotropy associated decrease in Morin temperature and superparamagnetic behavior was observed. Polysaccharide on the nanoparticle surface provided aqueous stability and low cytotoxicity. Starch coated nanoparticles was utilized to build polysaccharide - collagen crosslinks, which supplemented natural crosslinks in collagen, without disturbing the conformation of collagen. The resulting fibrillar lamellae showed a striking resemblance to native lamellae, but had a melting and denaturation temperature higher than native collagen. The biocompatibility and superparamagnetism of the nanoparticles also come handy in the development of stable collagen constructs for various biomedical applications, including that of MRI contrast agents.