Mechanistic Insights into Sphingomyelin Nanoemulsions as Drug Delivery Systems for Non-Small Cell Lung Cancer Therapy

纳米载体 细胞凋亡 A549电池 细胞毒性 药物输送 毒性 癌细胞 程序性细胞死亡 药理学 化学 癌症研究 细胞生物学 药品 生物 癌症 体外 生物化学 遗传学 有机化学
作者
Emma Ramos Docampo,Jenifer García-Fernández,Inés Mármol,Irene Morín-Jiménez,Maria Iglesias Baleato,María de la Fuente
出处
期刊:Pharmaceutics [Multidisciplinary Digital Publishing Institute]
卷期号:17 (4): 461-461 被引量:1
标识
DOI:10.3390/pharmaceutics17040461
摘要

Sphingomyelin nanoemulsions (SNs) are promising drug delivery systems with potential for treating challenging tumors, including non-small cell lung cancer (NSCLC), which has a poor prognosis and a 5-year survival rate below 5%. Understanding the toxicity mechanisms and intracellular behavior of SNs is crucial for optimizing their therapeutic application. This study aims to investigate the interaction between SNs and A549 lung adenocarcinoma cells, focusing on their cytotoxic effects and mechanisms of cellular toxicity. SNs were synthesized and characterized for size, surface charge, and stability. A549 cells were treated with varying concentrations of SNs, and cellular uptake pathways were assessed using inhibitors of energy-dependent processes. Cytotoxicity was evaluated through an alamarBlue assay to determine the IC50 value after 24 h. Mechanisms of toxicity, including lysosomal and mitochondrial involvement, were examined using co-localization studies, mitochondrial membrane potential assays, and markers of apoptosis. SNs exhibited rapid cellular uptake via energy-dependent pathways. The IC50 concentration for A549 cells was 0.89 ± 0.15 mg/mL, suggesting favorable cytocompatibility compared to other nanocarriers. At IC50, SNs induced apoptosis characterized by lysosomal damage, mitochondrial membrane permeabilization, and the release of apoptotic factors. These effects disrupted autophagic flux and contributed to cell death, demonstrating potential for overcoming drug resistance. Resveratrol-loaded SNs showed enhanced cytotoxicity, supporting their application as targeted drug delivery vehicles. This study highlights the potential of SNs as efficient drug delivery systems for NSCLC therapy, offering insights into their cellular interactions and toxicity mechanisms. These findings pave the way for the rational design of SN-based therapeutic platforms for cancer and other mitochondria-related diseases.

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