Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers

Carola F. Díaz, Diego L. Cifuentes, Maximiliano Oyarzún, Verónica A. Jiménez, Leonardo Guzmán

Research output: Contribution to journalArticlepeer-review

Abstract

Surface-modified PAMAM dendrimers have important applications in drug delivery, yet a gap remains about the role that surface functionalization plays on their cell internalization capacity. We examined the cell internalization kinetics of PAMAM dendrimers that were surface-modified with acetyl, folate and poly(ethylene glycol), as model functional groups differing in size, charge, and chemical functionality. Dendrimers with 25% functionalization were internalized by HEK cells, but with slower rates and lower maximum uptakes than the native dendrimer between 1-6 h of incubation. Dendrimers with 50% functionalization exhibited negligible internalization capacities at all incubation times. Molecular dynamics simulations revealed that the solvent accessibility of the cationic surface charges is a key factor affecting cell internalization, unlike the total charge, functionality or size of surface-modified PAMAM dendrimers. These findings provide valuable insights to assist the design of PAMAM-based systems for drug delivery applications.

Original languageEnglish
Pages (from-to)7782-7790
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume21
Issue number38
DOIs
Publication statusAccepted/In press - 2023

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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