TY - JOUR
T1 - Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers
AU - Díaz, Carola F.
AU - Cifuentes, Diego L.
AU - Oyarzún, Maximiliano
AU - Jiménez, Verónica A.
AU - Guzmán, Leonardo
N1 - Publisher Copyright:
© 2023 The Royal Society of Chemistry
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85172261073&partnerID=8YFLogxK
U2 - 10.1039/d3ob01265d
DO - 10.1039/d3ob01265d
M3 - Article
C2 - 37705355
AN - SCOPUS:85172261073
SN - 1477-0520
VL - 21
SP - 7782
EP - 7790
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 38
ER -