Current drug delivery · 2026
Preparation of Dual-Drug-Loaded Liver-Targeted Liposomes Co-Modified with SP94 Peptide and TAT Peptide.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Jing Lin, Luo Simei, Gan Ye, Li Lili, Wu Haotian, Zhang Jiajia, Liu Xu, Yuan Mingqing
Аннотация
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 < 0.2, size change < 10%) and in 50% fetal bovine serum (FBS) for 24 hours (transmittance > 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.
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 < 0.2, size change < 10%) and in 50% fetal bovine serum (FBS) for 24 hours (transmittance > 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.