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Development and Characterization of PEGylated β-Carotene-Loaded Liposomes as Radiosensitizers in HepG2 Hepatocellular
Habiba Abdel-Moamen1, Eman R Abbase1, Manal F El-Khadragy2
1Department of Physics, Medical Biophysics Division, Faculty of Science, HELWAN University, Cairo, Egypt.
Introduction:
Hepatocellular Carcinoma (HCC) is a leading cause of cancer death with limited responsiveness to radiotherapy. β-Carotene has chemopreventive properties, but its clinical use is hindered by poor aqueous solubility and instability. This study developed PEGylated β-carotene-loaded liposomes (PEGLipo- β-Car) as a novel nanocarrier-based radiosensitizer and used in silico modeling to explore its molecular interactions.
Methods:
PEG-Lipo-β-Car was prepared via thin-film hydration and characterized (TEM, DLS, FTIR, DSC). Cytotoxicity and radiosensitization were evaluated in HepG2 cells under γ-irradiation (0, 5, 10 Gy) using MTT assays, with synergy quantified via Combination Indices (CI). Molecular docking assessed β-carotene binding to PARP and ATM.
Results:
PEG-Lipo-β-Car exhibited good colloidal stability (size: 143.4 ± 8.2 nm, PDI: 0.201, EE >94%). At 10 Gy irradiation, it reduced the IC50 from 29.78 to 0.57 μg/mL, a 52-fold enhancement with strong synergy (CI=0.019). Empty liposomes alone conferred significant radiosensitization (~30-fold). Docking revealed β- carotene binds the catalytic sites of PARP (-9.19 ± 0.37 kcal/mol) and ATM (-10.12 ± 0.36 kcal/mol).
Discussion:
The observed radiobiological synergy may stem from a combined effect of carrier-mediated membrane perturbation and/or ROS amplification, coupled with the potential inhibition of DNA repair pathways by the delivered β-carotene.
Conclusions:
PEGylation enhances β-carotene's stability and radiosensitizing efficacy in HCC cells through a combined mechanism involving carrier effects and potential interference with PARP- and ATM-mediated DNA repair. PEG-Lipo-β-Car is a promising candidate for future preclinical evaluation in hepatocellular carcinoma radiotherapy.
