Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 143, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112157
Keywords
Anthocyanins; Algae membrane lipids; Lipid-based nanocarrier; Mitochondria-targeted therapy; Nanomedicine
Funding
- PT national funds (FCT/MCTES, Fundacao para a Ciencia e Tecnologia and Ministerio da Ciencia, Tecnologia e Ensino Superior) [UIDB/50006/2020]
- FCT (Fundacao para a Ciencia e Tecnologia) [SFRH/BD/138206/2018]
- ESF (European Social Fund) through POCH (Programa Operacional Capital Humano) [SFRH/BD/138206/2018]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/138206/2018] Funding Source: FCT
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The innovative SC-Nanophytosomes developed with mitochondriotropic elderberry anthocyanin-enriched extract and self-assembling membrane polar lipids from Codium tomentosum show potential in targeting mitochondria and improving mitochondrial function, as well as enhancing cellular resistance to toxins.
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 mu M 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 degrees C. 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.
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