Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.
Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au(0))(51.2)-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au(0))(51.2-)G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs.
Shi
Xiangyang
X
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, 2999 North Renmin Road, Shanghai 201620, People's Republic of China. xshi@dhu.edu.cn
Wang
Su He
SH
Lee
Inhan
I
Shen
Mingwu
M
Baker
James R
JR
D000970:Antineoplastic Agents / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000378:metabolism*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D004705:Endocytosis; D005029:Ethylenediamines / Q000737:chemistry; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007624:KB Cells; D007700:Kinetics; D053768:Metal Nanoparticles / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011073:Polyamines / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000737:chemistry
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D002352:Carrier Proteins; D050091:Dendrimers; D005029:Ethylenediamines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; C104700:PAMAM Starburst; D011073:Polyamines; D011956:Receptors, Cell Surface; D006046:Gold; D005492:Folic Acid; D013890:Thiourea