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Glycyrrhetinic Acid-Modified Norcantharidin Nanoparticles for Active Targeted Therapy of Hepatocellular Carcinoma

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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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Keywords: ACTIVE TARGETING; GLYCYRRHETINIC ACID; HEPATOCELLULAR CARCINOMA; NANOPARTICLE; NORCANTHARIDIN

Document Type: Research Article

Publication date: January 1, 2018

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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