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.