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

Abstract

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.

Liver fibrosis: pathological features, clinical treatment and application of therapeutic nanoagents

“…175 In addition, the ease of functionalization of the surface of metal oxide nanoparticles, as well as their inherent properties, provide some advantages and new insights for re-examining the treatment of liver fibrosis. Ferric oxide nanoparticles (Fe 3 O 4 NPs) 176 are more suitable for liver imaging due to their enhanced transverse relaxation properties. Cerium oxide nanoparticles (CeO 2 NPs) 177 and zinc oxide nanoparticles (ZnO NPs) 178 Moreover, the expression of CTGF and collagen production were significantly reduced, which provided a foundation for future in vivo studies.…”

Nanotechnology in Drug Delivery for Liver Fibrosis

“…Meanwhile, the dendrimer did not show hepatic or renal toxicity, or immunotoxicity, suggesting it may be a safe and efficient hepatocyte-targeting delivery platform. Similarly, pullulan stabilized iron oxide nanoparticles (P-SPIONs) targeting ASGPR were designed for theranostic application of liver diseases ( Saraswathy et al, 2021 ). P-SPIONs showed early diagnosis of liver fibrosis in rodent model.…”

MRI Contrast Agents in Glycobiology

“…These two experiments underlined the ASGP-R mediated targeting of P-SPIO-AT to the fibrotic liver. A current of 400 A on an aqueous solution of 5 mg/mL of P-SPIO-AT raised the temperature above 50 °C, to facilitate effective hyperthermia [ 113 ].…”