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Updated: Dec 31, 2025
Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
Published on: November 17, 2015
Biological response and cytotoxicity induced by lipid nanocapsules
Marzena Szwed1, Maria Lyngaas Torgersen1, Remya Valsala Kumari2
1Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
Background:
Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of Labrafac™ Lipophile WL1349, Lipoid® S75 and Solutol® HS15.
Results:
High resolution SIM microscopy showed that the DiD-labeled LNCs ended up in lysosomes close to the membrane. Empty LNCs, i.e. without encapsulated drug, induced not only increased lysosomal pH, but also acidification of the cytosol and a rapid inhibition of protein synthesis. The cytotoxicity of the LNCs were measured for up to 72 h of incubation using the MTT assay and ATP measurements in all three cell lines, and revealed that MDA-MB-468 was the most sensitive cell line and MCF-7 the least sensitive cell line to these LNCs. The LNCs induced generation of reactive free oxygen species and lipid peroxidation. Experiments with knock-down of kinases in the near-haploid cell line HAP1 indicated that the kinase HRI is essential for the observed phosphorylation of eIF2α. Nrf2 and ATF4 seem to play a protective role against the LNCs in MDA-MB-231 cells, as knock-down of these factors sensitizes the cells to the LNCs. This is in contrast to MCF-7 cells where the knock-down of these factors had a minor effect on the toxicity of the LNCs. Inhibitors of ferroptosis provided a large protection against LNC toxicity in MDA-MB-231 cells, but not in MCF-7 cells.
Conclusions:
High doses of LNCs showed a different degree of toxicity on the three cell lines studied, i.e. MCF-7, MDA-MD-231 and MDA-MB-468 and affected signaling factors and the cell fate differently in these cell lines.
Insights
Lipid nanocapsules (LNCs) exhibit varying toxicity in breast cancer cells, impacting protein synthesis and causing oxidative stress. Cell sensitivity differs, with MDA-MB-468 being most susceptible, highlighting the need for careful LNC drug delivery design.
Area of Science:
- Nanotechnology
- Cell Biology
- Drug Delivery
Background:
- Lipid nanocapsules (LNCs) are advanced drug delivery systems.
- Cellular toxicity mechanisms of LNCs remain largely uncharacterized.
- Investigating LNCs composed of Labrafac™ Lipophile WL1349, Lipoid® S75, and Solutol® HS15.
Purpose of the Study:
- To elucidate the mechanisms of LNC-induced toxicity in breast cancer cell lines.
- To compare the sensitivity of MCF-7, MDA-MD-231, and MDA-MB-468 cells to LNCs.
- To identify cellular pathways involved in LNC intoxication.
Main Methods:
- Confocal microscopy (SIM) to track LNC localization.
- MTT assay and ATP measurements for cytotoxicity assessment.
- Gene knockdown experiments (HRI, Nrf2, ATF4) and ferroptosis inhibition.
Main Results:
- LNCs accumulate in lysosomes, increase lysosomal pH, acidify cytosol, and inhibit protein synthesis.
- MDA-MB-468 cells showed highest sensitivity, MCF-7 the least.
- LNCs induce reactive oxygen species and lipid peroxidation; HRI kinase is crucial for eIF2α phosphorylation.
Conclusions:
- LNCs exhibit differential toxicity and affect cellular signaling and fate distinctively across MCF-7, MDA-MD-231, and MDA-MB-468 cell lines.
- Nrf2 and ATF4 play a protective role in MDA-MB-231 cells, while ferroptosis inhibition offers protection in these cells but not MCF-7.
- Understanding these mechanisms is critical for optimizing LNC-based therapeutics.
