A Novel Nanoscale Phase-Change Contrast Agent Evaluates the Hepatic Fibrosis Through Targeting Hepatic Stellate Cell Platelet-Derived Factor Beta Receptor by Ultrasound in Vitro

Objective

As a reversible condition at its early stages, liver fibrosis can progress to cirrhosis and hepatocellular carcinoma, underscoring the importance of early detection for preventing severe outcomes and improving prognosis. To address this issue, we developed a platelet-derived growth factor receptor β (PDGFRβ)-targeted nanoscale phase-change contrast agent to target activated hepatic stellate cells (aHSC) and enable ultrasound imaging as a foundation for the early evaluation of liver fibrosis.

Methods

PDGFR-β antibody-modified phase-change contrast agents (PPCAs) were synthesized utilizing film hydration and ultrasonic emulsification with perfluoropentane (PFP) encapsulated. PPCAs were specifically conjugated to aHSC with high PDGFR-β expression, whose targeting ability was evaluated using fluorescence confocal microscopy and flow cytometry. Phase transition at different temperatures and mechanical indices (MIs), as well as contrast-enhanced ultrasound imaging were analyzed.

Results

PPCAs had an average diameter of 283.6 ± 11.3 nm with good dispersibility and relative stability, and the echo intensity increased correspondingly with increasing MIs. PPCAs exhibited both excellent biocompatibility and imaging ability when excited by high-frequency ultrasound set to an MI of 1.0 at 37°C, and simultaneously showed strong specific targeting ability to aHSC, with cellular uptake reaching 56.67 ± 5.96%.

Conclusion

As a new imaging avenue, PPCAs have the potential to enhance ultrasound imaging and establish the basis for diagnosis by targeting aHSC specifically with good biocompatibility and stability.