Retinoic acid‐conjugated chitosan/manganese porphyrin ionic‐complex nanoparticles for improved T₁ contrast MR imaging of hepatic fibrosis

Abstract Noninvasive and precise diagnosis of hepatic fibrosis is very important for the preventive therapeutic regimen of hepatic cirrhosis and cancer. In this study, we fabricated T₁ contrast Mn‐porphyrin (MnTPPS₄)/retinoic acid‐chitosan ionic‐complex nanoparticles (MRC NPs). The functional properties of MRC NPs were evaluated via transmission electron microscopy (TEM) imaging, release study, cytotoxicity assay, hepatocyte‐specific uptake assay, and magnetic resonance (MR) imaging study. TEM images confirmed the typical structure of an ionic‐complex NPs with around 100–200 nm of diameter. MnTPPS₄ is released from MRC NPs for up to 24 hr in controlled pattern which implies that more reliable and convenient hepatic MR imaging is possible using of MRC NPs in clinical practice. Hepatocytes uptake assay proved retinoic acid‐specific targeting of MRC NPs. The same results were observed in animal pharmacokinetic studies. In vitro MR phantom study, MRC NPs showed an increased T₁ relaxivity (r₁ = 6.772 mM⁻¹ s⁻¹) in comparison with 3.242 mM⁻¹ s⁻¹ of MnTPPS₄. The result was confirmed again in vivo MR imaging studies. Taken together, MRC NPs displayed a potential for noninvasive diagnostic T₁ MR imaging of hepatic fibrosis with improved target specificity and prolonged MR imaging time window.