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  • Title: Glycyrrhetinic Acid-Modified Norcantharidin Nanoparticles for Active Targeted Therapy of Hepatocellular Carcinoma.
    Author: Zhang H, Jiang Y, Ni X, Chen L, Wu M, Liu J, Yang B, Shan X, Yang L, Fan J, Chen Y, Wu J, Fu S.
    Journal: J Biomed Nanotechnol; 2018 Jan 01; 14(1):114-126. PubMed ID: 29463369.
    Abstract:
    Norcantharidin (NCTD), the demethylated analogue of cantharidin, has been confirmed to have a good anti-tumor effect against hepatocellular carcinoma (HCC). However, its use is limited by its poor water solubility and low tumortargeting efficacy. In the present study, an active-targeted drug delivery nanoplatform was designed to deliver NCTD using a glycyrrhetinic acid (GA)-decorated copolymer (mPEG-PCL-PEI-GA, MPG). The NCTD-loaded polymeric nanoparticles (MPG/NCTD) formed by self-assembly in water exhibited a mean hydrodynamic diameter of roughly 89 nm. In vitro studies revealed that GA-conjugated nanoparticles (AT NPs) had superior cytotoxicity and higher targeting efficacy on HepG2 cells compared to non-conjugated nanoparticles (Non-AT NPs, NAT NPs). Determination of cell apoptosis and cell cycle phase showed that AT NPs resulted in increased cell apoptosis and a distinct increase in the G2 phase (65.30 ± 3.52%, P < 0.01) and S phase (46.39 ± 1.39%, P < 0.01). Evaluation of in vivo anti-tumor activity showed that the AT NPs significantly inhibited tumor growth and prolonged survival of tumor-bearing mice. The expression of Ki-67 and CD31 revealed that AT NPs inhibited cell proliferation and resulted in a decreased microvessel density (MVD). The results indicated that NCTD-loaded GA-modified nanoparticles may have great potential in HCC-targeted therapy.
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