Surface Modification of PAMAM Dendrimers Modulates the Mechanism of Cellular Internalization

详细信息    查看全文

• 作者：Angkana Saovapakhiran ; Antony D’ ; Emanuele ; David Attwood ; Jeffrey Penny
• 刊名：Bioconjugate Chemistry
• 出版年：2009
• 出版时间：April 15, 2009
• 年：2009
• 卷：20
• 期：4
• 页码：693-701
• 全文大小：261K
• 年卷期：v.20,no.4(April 15, 2009)
• ISSN：1520-4812

文摘

The aim of this study was to investigate the influence of dendrimer surface properties on cellular internalization and intracellular trafficking in the human colon adenocarcinoma HT-29 cell line. Third-generation (G3) polyamidoamine (PAMAM) dendrimers were modified to contain either two lauroyl chains (G3L2), two propranolol molecules (G3P2), or two lauroyl and two propranolol molecules (G3L2P2) at the dendrimer surface. Surface-modified and unmodified dendrimers were labeled with fluorescein isothiocyanate (FITC) at an average molar ratio of 1:1. The mechanisms of cellular internalization and intracellular trafficking of dendrimers were analyzed by confocal laser scanning microscopy and flow cytometry. The internalization of G3 and G3P2 dendrimers involved both caveolae-dependent endocytosis and macropinocytosis pathways; internalization of G3L2P2 dendrimer appeared to involve caveolae-dependent, and possibly clathrin-dependent, endocytosis pathways; and internalization of G3L2 dendrimer occurred via caveolae-dependent, clathrin-dependent, and macropinocytosis pathways. Subcellular colocalization data indicated that unmodified and all surface-modified G3 PAMAM dendrimers were internalized and trafficked to endosomes and lysosomes. It is therefore apparent that the initial mode of dendrimer internalization into HT-29 cells is influenced by the surface properties of G3 PAMAM dendrimer.