The uptake and intracellular fate of PLGA nanoparticles in epithelial cells

Abstract Biodegradable polymer nanoparticles (NPs) are a promising approach for intracellular delivery of drugs, proteins, and nucleic acids, but little is known about their intracellular fate, particularly in epithelial cells, which represent a major target. Rhodamine-loaded PLGA (polylactic-co-gly...

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Bibliographic Details
Published in:Biomaterials 2009-05, Vol.30 (14), p.2790-2798
Main Authors: Cartiera, Malgorzata S, Johnson, Katherine M, Rajendran, Vanathy, Caplan, Michael J, Saltzman, W. Mark
Format: Article
Language:English
Subjects:
Advanced Basic Science
Cell Line
Confocal microscopy
Dentistry
Epithelial cell
Epithelial Cells - metabolism
Humans
Intracellular
Intracellular Space - metabolism
Lactic Acid - chemistry
Lactic Acid - metabolism
Microscopy, Electron, Scanning
Nanoparticle
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Organelle
PLGA
Polyglycolic Acid - chemistry
Polyglycolic Acid - metabolism
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Summary:Abstract Biodegradable polymer nanoparticles (NPs) are a promising approach for intracellular delivery of drugs, proteins, and nucleic acids, but little is known about their intracellular fate, particularly in epithelial cells, which represent a major target. Rhodamine-loaded PLGA (polylactic-co-glycolic acid) NPs were used to explore particle uptake and intracellular fate in three different epithelial cell lines modeling the respiratory airway (HBE), gut (Caco-2), and renal proximal tubule (OK). To track intracellular fate, immunofluorescence techniques and confocal microscopy were used to demonstrate colocalization of NPs with specific organelles: early endosomes, late endosomes, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus. Confocal analysis demonstrated that NPs are capable of entering cells of all three types of epithelium. NPs appear to colocalize with the early endosomes at short times after exposure (∼2 h), but are also found in other compartments within the cytoplasm, notably Golgi and, possibly, ER, as time progressed over the period of 4–24 h. The rate and extent of uptake differed among these cell lines: at a fixed particle/cell ratio, cellular uptake was most abundant in OK cells and least abundant in Caco-2 cells. We present a model for the intracellular fate of particles that is consistent with our experimental data.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2009.01.057