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

Ariya Saraswathy,Nirmala Nimi,Ramapurath S Jayasree,P R Harikrishna Varma,Francis Boniface Fernandez,Sabareeswaran Arumugam,Marina Victor,Parvathy Radhakrishnapillai Suma,Shaiju S Nazeer,Sachin J Shenoy,Hema Santhakumar,Kunnumpurathu Jibin

doi:10.1038/s41598-021-97808-0

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.

Highlights

Diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes
A simple synthesis route was adopted for the formulation of P-super paramagnetic iron oxide nanoparticles (SPIONs) to develop a hepatocyte-specific MR contrast and hyperthermia agent
The thermal degradation of pullulan in P-SPIONs was shifted to 183 °C with a weight loss of 4% and the complete dissociation was observed after 625 °C with a total weight loss (12%) (Fig. 1e).The shift in the degradation peaks of pullulan in the coated system corresponds to catalytic behavior of the iron oxide core

Summary

Introduction

Diagnosis and therapy of liver fibrosis is of utmost importance, especially considering the increased incidence of alcoholic and non-alcoholic liver syndromes. Even though MRI provides images with intrinsic contrast, authentic diagnosis of diseases like liver associated malignancies often requires the use of external agents to enhance the image contrast for better visualization. Transverse relaxation of protons ( T2) is preferred over longitudinal relaxation ( T1) This is due to low T 1 response of accumulated fat within liver than hepatocytes[4]. Due to this reason, contrast agents with enhanced transverse relaxivity such as surface modified super paramagnetic iron oxide nanoparticles (SPIONs) are preferred for liver imaging over conventional gadolinium-based contrast agents with longitudinal relaxation properties. It is reported that low molecular weight polymer coatings have a tendency to cause osmotic nephropathy that leads to chronic renal failure[7,9]

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Results

Conclusion