Ultrasound molecular imaging with cRGD-PLGA-PFOB nanoparticles for liver fibrosis staging in a rat model

Abstract

Hepatic fibrosis is the only chronic liver disease process that can be reversed. Developing non-invasive and effective methods to quantitatively assess the degree of liver fibrosis is of great clinical significance and remains a major challenge. The key factors in hepatic fibrosis pathogenesis are the activation and proliferation of hepatic stellate cells that subsequently express integrin αvβ3. An ultrasound (US) agent combined with a targeting peptide may be used for the early and non-invasive diagnosis of hepatic fibrosis. Herein, we report the synthesis of core-shell nanoparticles (NPs) successfully engineered by conjugation with cyclic arginine-glycine-aspartic acid (cRGD) octapeptide, allowing hepatic integrin αvβ3 targeting for liver fibrosis staging. This system consists of a perfluorooctyl bromide (PFOB) liquid in the core that is stabilized with a Poly (lactic-co-glycolic acid) (PLGA) polymer shell and modified with a cRGD. These core-shell NPs (cRGD-PLGA-PFOB NPs) exhibited useful US molecular imaging features including high imaging contrast among liver fibrotic stages and the adjacent tissues. Our results indicate that the cRGD-PLGA-PFOB NPs have significant potential to distinguish different liver fibrotic stages and could be used in clinical applications.

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

“…Indeed, HSCs can interact with ECM proteins via α v β 3 integrin which binds to (arginine- glycine- aspartic acid) RGD domains on ECM proteins. α v β 3 integrin expression is upregulated during liver fibrosis development and progression ( 16 ) and ECM-α v β 3 interactions have been suggested to support HSC proliferation ( 17 ). Initiation and perpetuation of HSC activation is modulated by complex cross-talk between liver cells, infiltrating immune cells and the ECM ( 18 , 19 ).…”

Advances on Nanomedicines for Diagnosis and Theranostics of Hepatic Fibrosis

“…Based on the similar targeting mechanism, a core–shell nanostructure that combined the cyclic RGD peptide and an ultrasound agent was introduce. [ 54 ] In this structure, perfluorooctyl bromide (PFOB) acted as a core and cyclic RGD‐modified poly(lacticco‐glycolic acid) (PLGA) as a shell. This nanoprobe was able to display great contrast echo intensity for the ultrasound images to distinguish fibrotic tissues from normal hepatic tissues.…”

<p>Perfluorocarbons-Based ¹⁹F Magnetic Resonance Imaging in Biomedicine</p>

“…Despite the recent advances in 19 FMR targeted imaging with PFC NPs, most studies focus on α v β 3 -integrin, 77 , 79 , 80 folate receptor (FR) 81 – 85 and vascular endothelial growth factor receptor 2 (VEGFR2) 86 , 87 as molecular targets to detect tumor angiogenesis, proliferation and certain cardiovascular disease ( Figure 2 ). 19 F MRI of brain tumor angiogenesis with integrin-targeted PFC NPs in mice carrying U87 glioblastoma achieved a 50% increase in signal in the targeted group.…”