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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Glycyrrhetinic Acid and TAT Peptide Modified Dual-functional Liposomes for Treatment of Hepatocellular Cancer

Author(s): Sixi Huang, Di Ren, Xinrong Wu, Ming Li, Xuesong Yu, Xiaoling Nie, Ying Wang* and Yan Wang*

Volume 20, Issue 27, 2020

Page: [2493 - 2505] Pages: 13

DOI: 10.2174/1568026620666200722110244

Price: $65

Abstract

Background: Surgery remains the front-line therapeutic strategy to treat early hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC patients are high. 10- Hydroxycamptothecin (10-HCPT) is a known anti-HCC agent but its poor solubility and bioavailability have limited its clinical use.

Objective: In this study, we developed a novel nanoliposome encapsulated 10-hydroxycamptothecin modified with glycyrrhetinic acid (GA) and TAT peptide (GA/TAT-HCPT-LP) for the treatment of HCC. Dual modified GA and TAT can enhance tumor targeting and tumor penetration.

Methods: The GA/TAT-HCPT-LP NPs were synthesized using the thin-film dispersion method. GA/TAT-HCPT-LP were characterized for particle size, zeta potential and morphology. Drug release from the GA/TAT-HCPT-LP liposomes was measured by dialysis. Cell-uptake was assessed by microscopy and flow cytometry. Cell proliferation, migration and apoptosis were measured to evaluate in vitro antitumor activity of GA/TAT-HCPT-LP via CCK-8 assays, Transwell assays, and flow cytometry, respectively. The in vivo distribution of GA/TAT-HCPT-LP was evaluated in HCC animal models. Tumor- bearing mouse models were used to assess the in vivo therapeutic efficacy of GA/TAT-HCPT-LP.

Results: The mean particle size and mean zeta potential of GA/TAT-HCPT-LP were 135.55 ± 2.76 nm and -4.57 ± 0.23 mV, respectively. Transmission electron micrographs (TEM) showed that the GA/TAT-HCPT-LP had a near spherical shape and a double-membrane structure. GA/TAT-HCPT-LP led to slow and continuous drug release, and could bind to HepG2 cells more readily than other groups. Compared to control groups, treatment with GA/TAT-HCPT-LP had a significantly large effect on inhibiting cell proliferation, tumor cell migration and cell apoptosis. In vivo assays showed that GA/TATHCPT- LP selectively accumulated in tumor tissue with obvious antitumor efficacy.

Conclusion: In conclusion, the synthesized GA/TAT-HCPT-LP could effectively target tumor cells and enhance cell penetration, highlighting its potential for hepatocellular cancer therapy.

Keywords: Liposomes, 10-hydroxycamptothecin, Glycyrrhetinic acid, TAT peptide, Hepatocellular cancer, Tumor-targeting.

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