Cyclic RGDfK- and Sulfo-Cy5.5-functionalized mPEG-PCL theranostic nanosystems for hepatocellular carcinoma

Abstract Sorafenib (SF) is a standard, clinically-recognized therapy for treating hepatocellular carcinoma (HCC) patients. However, as a multikinase inhibitor, SF causes a systemic side effect. Therefore, there is an urgent need to selectively deliver the optimum dose of SF to the tumor site. The present study aimed to selectively target SF to HCC using a biocompatible drug carrier to increase the therapeutic efficacy, in turn, minimize the adverse effects. To this end, methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) di-block copolymer was selected as an amphiphilic carrier for SF that hydrophobic PCL core can encapsulate SF through self-assembly. Cyclic RGDfK (cRGD) was conjugated to the end of PEG-PCL (cRGD-PEG-PCL) for HCC targeting. Sulfo Cyanine 5.5 (S-Cy5.5) was also incorporated to PEG-PCL (S-Cy5.5-PEG-PCL) for near infrared fluorescence imaging. The composition, morphology and size distribution of nanoparticles (NPs) were characterized by 1H NMR, transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In addition, the ability of the integrin-mediated targeting of NPs for the selective delivery of SF was systemically investigated with Hep3B cell line and a nude mouse xenograft model. Consequently, it was found that S-Cy5.5-cRGD-PEG-PCL leads to the selective accumulation of SF into the tumor site and improve anticancer activity against HCC.