How does the cell overcome LCP nanoparticle-induced calcium toxicity?
Yu-Cheng Tseng1, Angela Yang, Leaf Huang
1Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-7571, United States.
Molecular Pharmaceutics
|September 17, 2013
Summary
Calcium (Ca2+) released by LCP nanoparticles is not toxic to cells. Functional calcium pumps in cell and mitochondrial membranes prevent cell death, even in vivo.
Area of Science:
- Cellular biology
- Nanotechnology
- Toxicology
Background:
- LCP nanoparticles can release calcium (Ca2+), raising concerns about potential cellular toxicity.
- Understanding cellular responses to nanoparticle-delivered calcium is crucial for safety assessments.
Purpose of the Study:
- To investigate the cellular mechanisms involved in responding to calcium (Ca2+) toxicity induced by LCP nanoparticles.
- To determine if LCP-delivered calcium poses a risk to cells in vitro and in vivo.
Main Methods:
- Conducted in vitro and in vivo studies using calcium (Ca2+) pump inhibitors.
- Utilized H460 cells to assess cellular responses to LCP nanoparticle exposure.
- Monitored cell viability and death pathways (apoptosis, necrosis).
Main Results:
- Elevated cytosolic calcium (Ca2+) was rapidly managed by Ca2+ pumps on plasma and mitochondrial membranes.
- Functional Ca2+ pumps effectively prevented LCP-induced apoptosis or necrosis.
- Inhibition of Ca2+ pumps led to necrosis in LCP-treated cells, both in vitro and in vivo.
Conclusions:
- Calcium (Ca2+) delivered by LCP nanoparticles is not inherently toxic to cells.
- Cellular Ca2+ pumps play a vital role in mitigating potential toxicity from LCP-delivered calcium.
- The presence of functional Ca2+ pumps ensures cell survival despite LCP nanoparticle exposure.
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