Bidooki Seyed Hesamoddin, Spitzer Lea, Petitpas Arnaud, Sánchez-Marco Javier, Martínez-Beamonte Roberto, Lasheras Roberto, Pellerin Virginie, Rodríguez-Yoldi María J, Navarro María Angeles, Osada Jesús, Fernandes Susana C M
Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Veterinaria, Instituto de Investigación Sanitaria de Aragón, Universidad de Zaragoza, C/Miguel Servet, 177, E-50013 Zaragoza, Spain.
Institute of Analytical Sciences and Physico-Chemistry for Environment and Materials (IPREM), E2S UPPA, CNRS, Université de Pau et des Pays de l'Adour, University Avenue, 64 012 Pau, France.
ACS Omega. 2024 Dec 16;9(52):51379-51393. doi: 10.1021/acsomega.4c08258. eCollection 2024 Dec 31.
The Mediterranean diet is a well-known dietary pattern that has gained considerable popularity worldwide for its ability to prevent the progression of nonalcoholic fatty liver disease. This is largely attributed to the use of virgin olive oil as the primary source of fat, which contains a substantial amount of squalene, a natural antioxidant. In order to enhance the delivery of squalene and amplify its effects due to its highly hydrophobic nature, herein, squalene has been incorporated into chitosan nanoparticles. The characterization of the resulting nanoparticles was conducted via scanning electron microscopy, dynamic light scattering, ζ potential, Fourier transform infrared spectroscopy, and gas chromatography-mass spectrometry. Reactive oxygen species (ROS) generation and cell viability assays were conducted in oxidative and endoplasmic reticulum (ER) stress in AML12 and a TXNDC5-deficient AML12 cell line, which was generated by CRISPR/Cas9 technology. The results demonstrated that squalene was successfully encapsulated in chitosan nanoparticles and exhibited rapid and efficient cellular uptake at a 150 μM squalene concentration within 48 h. In conclusion, the encapsulation of squalene in chitosan nanoparticles, compared to the poly(d,l-lactide--glycolic acid) and ethanol drug carriers, significantly enhanced its cellular uptake. This allows the administration of higher doses, which improve hepatocyte viability and reduce ROS levels, effectively compensating for the adverse effects of TXNDC5 deficiency under the context of hepatocyte stress protection.
地中海饮食是一种著名的饮食模式，因其能够预防非酒精性脂肪性肝病的进展而在全球范围内广受欢迎。这在很大程度上归因于使用初榨橄榄油作为主要脂肪来源，初榨橄榄油含有大量的角鲨烯，一种天然抗氧化剂。由于角鲨烯具有高度疏水性，为了增强其递送并放大其效果，本文将角鲨烯掺入壳聚糖纳米颗粒中。通过扫描电子显微镜、动态光散射、ζ电位、傅里叶变换红外光谱和气相色谱 - 质谱对所得纳米颗粒进行表征。在AML12细胞系和通过CRISPR/Cas9技术构建的TXNDC5缺陷型AML12细胞系中，进行活性氧（ROS）生成和细胞活力测定，以检测氧化应激和内质网（ER）应激。结果表明，角鲨烯成功包封在壳聚糖纳米颗粒中，并在48小时内以150μM角鲨烯浓度表现出快速有效的细胞摄取。总之，与聚（d，l - 丙交酯 - 乙交酯）和乙醇药物载体相比，壳聚糖纳米颗粒包封角鲨烯显著增强了其细胞摄取。这使得能够给予更高剂量，从而提高肝细胞活力并降低ROS水平，在肝细胞应激保护的背景下有效补偿TXNDC5缺陷的不利影响。
