Dendrimer internalization and intracellular trafficking in living cells

The ability of dendrimers to cross cell membranes is of much interest for their application in drug and gene delivery. Recent studies demonstrate that dendrimers are capable to enter cells by endocytosis, but the intracellular pathway following their internalization remains controversial. In this st...

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Vydáno v:Molecular pharmaceutics Ročník 7; číslo 3; s. 680
Hlavní autoři: Albertazzi, Lorenzo, Serresi, Michela, Albanese, Alberto, Beltram, Fabio
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 07.06.2010
Témata:
Animals
Biological Transport - physiology
Cell Line
Chromatography, Gel
Dendrimers - chemistry
Dendrimers - metabolism
Endocytosis - physiology
Flow Cytometry
HeLa Cells
Hep G2 Cells
Humans
Microscopy, Fluorescence
PC12 Cells
Rats
Spectrometry, Fluorescence
ISSN:1543-8392, 1543-8392
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Shrnutí:The ability of dendrimers to cross cell membranes is of much interest for their application in drug and gene delivery. Recent studies demonstrate that dendrimers are capable to enter cells by endocytosis, but the intracellular pathway following their internalization remains controversial. In this study we use confocal fluorescence microscopy to elucidate the intracellular trafficking properties of PAMAM dendrimers with high spatial and temporal resolution in living HeLa cells. Macromolecules of different chemical functionality (neutral, cationic and lipidated), size (from G2 up to G6) and surface charge are investigated and their internalization properties correlated with the molecular structure. Toxicity and internalization data are discussed that allow the identification of dendrimers maximizing intracellular uptake with the minimum effect on cell viability. Time-lapse imaging and colocalization assays with fluorescent biomarkers for endocytic vesicles demonstrate that dendrimers are internalized by both clathrin-dependent endocytosis and macropinocytosis and are eventually delivered to the lysosomal compartment. Moreover we analyzed the uptake of dendrimers in additional cell lines of practical interest for therapeutic purposes. These measurements together with a direct comparison with TAT peptides demonstrate that PAMAM dendrimers possess similar properties to these widely used cell-penetrating peptides and thanks to their chemical tunability may represent a valid alternative for drug and gene delivery.
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ISSN:1543-8392
1543-8392
DOI:10.1021/mp9002464