Document Detail

Dendrimer internalization and intracellular trafficking in living cells.
MedLine Citation:
PMID:  20394437     Owner:  NLM     Status:  MEDLINE    
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.
Lorenzo Albertazzi; Michela Serresi; Alberto Albanese; Fabio Beltram
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  7     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-09-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  680-8     Citation Subset:  IM    
NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, I-56127 Pisa, Italy.
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MeSH Terms
Biological Transport / physiology
Cell Line
Chromatography, Gel
Dendrimers / chemistry,  metabolism*
Endocytosis / physiology
Flow Cytometry
Hela Cells
Hep G2 Cells
Microscopy, Fluorescence
PC12 Cells
Spectrometry, Fluorescence
Reg. No./Substance:
0/Dendrimers; 0/PAMAM Starburst

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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