Cyclic RGDfK- and Sulfo-Cy5.5-functionalized mPEG-PCL theranostic nanosystems for hepatocellular carcinoma
| Autor: | Ji Sun Park, Gilson Khang, Jee Yoon Park, Heung Jae Chun, Yeong Jun Song, Dae Hyeok Yang, Kyeongsoon Park, Su Jung You, Jae Kwang Kim |
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| Rok vydání: | 2021 |
| Předmět: |
Sorafenib
Side effect biology Chemistry General Chemical Engineering technology industry and agriculture macromolecular substances 02 engineering and technology Conjugated system 010402 general chemistry 021001 nanoscience & nanotechnology medicine.disease biology.organism_classification 01 natural sciences 0104 chemical sciences Nude mouse Dynamic light scattering Hepatocellular carcinoma Cancer research medicine Distribution (pharmacology) 0210 nano-technology Drug carrier medicine.drug |
| Zdroj: | Journal of Industrial and Engineering Chemistry. 99:204-213 |
| ISSN: | 1226-086X |
| Popis: | 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-Cyanine5.5 (S-Cy5.5) was also incorporated to PEG-PCL (S-Cy5.5-PEG-PCL) for near-infrared fluorescence (NIRF) 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. |
| Databáze: | OpenAIRE |
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