What question did this study set out to answer?

The aim is to create liposomes modified with SP94 and TAT peptides to enhance targeting and effectiveness against liver cancer.

January 18, 2026

Preparation of Dual-Drug-Loaded Liver-Targeted Liposomes Co-Modifiedwith SP94 Peptide and TAT Peptide

Key Points

The aim is to create liposomes modified with SP94 and TAT peptides to enhance targeting and effectiveness against liver cancer.
Developed dual-peptide (SP94/TAT) co-modified liposomes for drug delivery.
Encapsulated docetaxel and doxorubicin via film dispersion and ammonium sulfate gradient.
Evaluated physicochemical properties, encapsulation efficiency, and stability of liposomes.
Conducted cytotoxicity assays and measured cellular uptake in vitro.
Optimized liposomes showed spherical shape with size of 119.6 nm and high encapsulation efficiency (DOX: 92.97%, DTX: 80.33%).
Demonstrated significant sustained release of drugs over 48 hours (68.2% DTX, 74.8% DOX).
Exhibited 2.3-fold higher cellular uptake in HepG2 versus single-modified liposomes.
Achieved a significantly lower IC50 value in cytotoxicity assays and increased apoptosis in HepG2 cells.

Abstract

Introduction: The toxicity of nontargeted chemotherapy hinders liver cancer treatment. This study developed dual-peptide (SP94/TAT) co-modified liposomes (SP94/TAT-DOX/DTX-LPs) for enhanced targeting and efficacy. Methods: Liposomes encapsulating docetaxel (DTX) and doxorubicin (DOX) were prepared via film dispersion/ammonium sulfate gradient using DSPE-PEG, lecithin, and cholesterol. SP94 (targeting) and TAT (penetrating) peptides were conjugated via organic phase reaction/insertion. Their physicochemical properties, encapsulation efficiency, stability, drug release, and in vitro antitumor activity were evaluated. Results: Optimized SP94/TAT-DOX/DTX-LPs were spherical (119.6 ± 4.1 nm; PDI 0.161 ± 0.006; zeta -9.84 ± 1.54 mV), and their encapsulation efficiency was high (DOX: 92.97 ± 1.73%; DTX: 80.33 ± 0.96%). Stability was confirmed at 4 °C for 30 days (PDI 90%). Sustained release showed 68.2 ± 3.5% (DTX) and 74.8 ± 2.9% (DOX) cumulative release at 48h (PBS pH 7.4). In vitro, SP94/TATDOX- LPs showed 2.3-fold higher HepG2 cellular uptake versus single-modified liposomes (p<0.001), with minimal LO2 uptake. Cytotoxicity assays revealed a 3.11-fold lower IC50 (0.096 ± 0.026 μg/mL) versus unmodified liposomes (0.299 ± 0.103 μg/mL). Apoptosis was significantly higher (39.5% in HepG2) than in single-modified formulations (20.55–26.74%). Discussion: SP94/TAT-LPs enable dual-stage targeting: SP94 targets liver cancer cells, and TAT enhances penetration, significantly improving in vitro antitumor activity. Study limitations include sole in vitro validation (HepG2/LO2), small sample size (n=3), parameter variability, and lack of in vivo data on targeting, pharmacokinetics, and toxicity. Conclusion: SP94/TAT-DOX/DTX-LPs achieved effective dual-stage targeting and synergistic cytotoxicity. High encapsulation, stability, and sustained release support their potential as a targeted platform for liver cancer therapy, reducing off-target toxicity.

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