HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb.
In the present study, we report the synthesis and human growth factor receptor-2 (HER2) specific tumor targeting properties of a dendrimer conjugated to anti-HER2 mAb (monoclonal antibody) conjugate. The polyamidoamine (PAMAM) dendrimer generation five (G5) was labeled with alexaFluor 488 and conjugated to anti-HER2 mAb. The binding and internalization of the antibody-conjugated dendrimer to HER2-expressing cells was evaluated by flow cytometry and confocal microscopy. Uniquely, the conjugate demonstrated cellular uptake and internalization in HER2-expressing cells as compared to free antibody. The time course of internalization and blocking experiments with free antibody suggest that the rapid and efficient cellular internalization of the dendrimer-antibody conjugate was achieved without alterations in specificity of targeting. Animal studies demonstrated that the conjugate targets HER2-expressing tumors.
Shukla
Rameshwer
R
Michigan Nanotechnology Institute for Medicine and Biological Sciences, Department of Internal Medicine, Division of Allergy, University of Michigan, 9220 MSRB III, Box 0648, Ann Arbor, 48109, USA.
Thomas
Thommey P
TP
Peters
Jennifer L
JL
Desai
Ankur M
AM
Kukowska-Latallo
Jolanta
J
Patri
Anil K
AK
Kotlyar
Alina
A
Baker
James R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D050091:Dendrimers; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism*; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D001672:Biocompatible Materials; D050091:Dendrimers; D005456:Fluorescent Dyes; D011073:Polyamines; D018719:Erb-b2 Receptor Tyrosine Kinases; C104700:PAMAM Starburst