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

[ Vol. 20 , Issue. 27 ]

Author(s):

Sixi Huang, Di Ren, Xinrong Wu, Ming Li, Xuesong Yu, Xiaoling Nie, Ying Wang* and Yan Wang*   Pages 2493 - 2505 ( 13 )

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.

Affiliation:

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006 Guangzhou, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006 Guangzhou, General Hospital of Southern Theater Command, PLA, 510006 Guangzhou, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, 510006 Guangzhou, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, 510006 Guangzhou, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006 Guangzhou, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, 510006 Guangzhou, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006 Guangzhou



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