The effect of surface functionality on cellular trafficking of dendrimers

Omathanu P. Perumal, Rajyalakshmi Inapagolla, Sujatha Kannan, Rangaramanujam M. Kannan

Research output: Contribution to journalArticlepeer-review

Abstract

Dendrimers are an emerging group of nanostructured, polymeric biomaterials that have potential as non-viral vehicles for delivering drugs and genetic material to intracellular targets. They have a high charge density with tunable surface functional groups, which can alter the local environment and influence cellular interactions. This can have a significant impact on the intracellular trafficking of dendrimer-based nanodevices. With the help of flow cytometry, fluorescence microscopy, and by using specific inhibitors, the influence of surface functionality on their uptake in A549 lung epithelial cells, and subsequent intracellular distribution was investigated. In this paper, we have shown that even though all the dendrimers are taken up by fluid-phase endocytosis, significant differences in uptake mechanisms exist. Anionic dendrimers appear to be mainly taken up by caveolae mediated endocytosis in A549 lung epithelial cells, while cationic and neutral dendrimers appear to be taken in by a non-clathrin, non-caveolae mediated mechanism that may be by electrostatic interactions or other non-specific fluid-phase endocytosis. These findings open up new possibilities of targeting therapeutic agents to specific cell organelles based on surface charge.

Original languageEnglish (US)
Pages (from-to)3469-3476
Number of pages8
JournalBiomaterials
Volume29
Issue number24-25
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

  • Cellular transport
  • Dendrimers
  • Drug delivery
  • Endocytosis
  • Hyperbranched polymers
  • PAMAM dendrimers

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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