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ACS Nano

Publication date: 2011-06-01
Pages: 4319 - 4328
Publisher: American Chemical Society

Author:

Van de Broek, Bieke
Devoogdt, Nick ; D'Hollander, Antoine ; Gijs, Hannah-Laura ; Jans, Karolien ; Lagae, Liesbet ; Muyldermans, Serge ; Maes, Guido ; Borghs, Gustaaf

Keywords:

branched gold nanoparticles, nanobody conjugation, specific cell targeting, photothermal therapy, domain antibody fragments, cancer-therapy, optical-properties, breast-cancer, au nanoparticles, sulfide nanoparticles, vascular-permeability, ovarian-cancer, tumor, nanocages, Science & Technology, Physical Sciences, Technology, Chemistry, Multidisciplinary, Chemistry, Physical, Nanoscience & Nanotechnology, Materials Science, Multidisciplinary, Chemistry, Science & Technology - Other Topics, Materials Science, DOMAIN ANTIBODY FRAGMENTS, CANCER-THERAPY, OPTICAL-PROPERTIES, BREAST-CANCER, AU NANOPARTICLES, SULFIDE NANOPARTICLES, VASCULAR-PERMEABILITY, OVARIAN-CANCER, TUMOR, NANOCAGES, Animals, Antibodies, Antigens, CHO Cells, Cell Line, Tumor, Cricetinae, Cricetulus, Gold, Humans, Hyperthermia, Induced, Lasers, Metal Nanoparticles, Nanoparticles, Nanostructures, Phototherapy, Prostate-Specific Antigen, Receptor, ErbB-2, Receptor, erbB-2

Abstract:

Branched gold nanoparticles are potential photothermal therapy agents because of their large absorption cross section in the near-infrared window. Upon laser irradiation they produce enough heat to destroy tumor cells. In this work, branched gold nanoparticles are blofunctionalized with nanobodies, the smallest fully functional antigen-binding fragments evolved from the variable domain, the VHH, of a camel heavy chain-only antibody. These nanobodies bind to the HER2 antigen which is highly expressed on breast and ovarian cancer cells. Flow cytometric analysis and dark field Images of HER2 positive SKOV3 cells incubated with anti-HER2 conjugated branched gold nanoparticles show specific cell targeting. Laser Irradiation studies reveal that HER2 positive SKOV3 cells exposed to the anti-HER2 targeted branched gold nanoparticles are destroyed after five minutes of laser treatment at 38 W/cm(2) using a 690 nm continuous wave laser. Starting from a nanoparticle optical density of 4, cell death is observed, whereas the control samples, nanoparticles with anti-PSA nanobodies, nanoparticles only, and laser only, do not show any cell death. These results suggest that this new type of bioconjugated branched gold nanoparticles are effective antigen-targeted photothermal therapeutic agents for cancer treatment.