REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, nº 228, Porto 4050-313, Portugal.
Chemistry Center - Vila Real (CQ-VR), Chemistry Department, School of Life and Environmental Sciences, University of Trás-os-Montes e Alto Douro, UTAD, P.O. Box 1013; 5001-801 Vila Real, Portugal.
Biomed Pharmacother. 2021 Nov;143:112157. doi: 10.1016/j.biopha.2021.112157. Epub 2021 Sep 10.
The development of nanomedicines to modulate the mitochondrial function is a great scientific challenge since mitochondrial dysfunction is a pathological hallmark of many chronic diseases, including degenerative brain pathologies like Parkinson's and Alzheimer's diseases. To address this challenge, the mitochondriotropic features of the elderberry anthocyanin-enriched extract (Sambucus nigra) were combined with the self-assembling properties of the membrane polar lipids from Codium tomentosum in an innovative SC-Nanophytosomes formulation. Membrane polar lipids, obtained by a new procedure as chlorophyll-free extract, are characterized by 26% of non-phosphorus polar lipids and 74% of phospholipids (dominated by anionic lipids) containing a high degree of polyunsaturated fatty acids. The anthocyanin-enriched extract is dominated by a mixture of four cyanidin-glycosides, representing about 86% of their phenolic content. SC-Nanophytosomes engineered with 600 µM algae membrane polar lipids and 0.5 mg/L of the anthocyanin-enriched extract are nanosized vesicles (diameter =108.74 ± 24.74 nm) with a negative surface charge (Zeta potential = -46.93 ± 6.63 mV) that exhibit stability during storage at 4 ºC. In vitro assays with SH-SY5Y cells showed that SC-Nanophytosomes have the competence to target mitochondria, improving the mitochondrial respiratory chain complexes I and II and preserving the mitochondrial membrane potential in the presence of rotenone. Additionally, SC-Nanophytosomes protect SH-SY5Y cells against the toxicity induced by rotenone or glutamate. Green-fluorescent labeled SC-Nanophytosomes were used to reveal that they are mainly internalized by cells via caveola-mediated endocytosis, escape from endosome and reach the cytoplasm organelles, including mitochondria. Overall, data indicate that SC-Nanophytosomes have the potential to support a mitochondria-targeted therapy for neurodegenerative diseases.
为了应对这一挑战，将接骨木果花色苷浓缩提取物（黑接骨木）的靶向线粒体特性与 Codium tomentosum 的膜极性脂质的自组装特性结合到一种创新的 SC-Nanophytosomes 制剂中。通过一种新的程序获得的膜极性脂质作为无叶绿素提取物，其特征在于非磷极性脂质占 26%，磷脂（主要为阴离子脂质）占 74%，含有高度多不饱和脂肪酸。花色苷浓缩提取物主要由四种矢车菊苷-糖苷的混合物组成，占其总酚含量的约 86%。用 600 µM 藻类膜极性脂质和 0.5 mg/L 花色苷浓缩提取物构建的 SC-Nanophytosomes 是纳米尺寸的囊泡（直径 = 108.74 ± 24.74nm），带负表面电荷（Zeta 电位 = -46.93 ± 6.63 mV），在 4°C 下储存时表现出稳定性。用 SH-SY5Y 细胞进行的体外试验表明，SC-Nanophytosomes 具有靶向线粒体的能力，可改善线粒体呼吸链复合物 I 和 II，并在鱼藤酮存在的情况下保持线粒体膜电位。此外，SC-Nanophytosomes 可保护 SH-SY5Y 细胞免受鱼藤酮或谷氨酸诱导的毒性。用绿色荧光标记的 SC-Nanophytosomes 揭示它们主要通过细胞内吞作用的 caveola 介导内吞作用被细胞内化，从内涵体逃逸并到达细胞质细胞器，包括线粒体。总体而言，数据表明 SC-Nanophytosomes 有可能支持针对神经退行性疾病的靶向线粒体治疗。
