title: Anti-Neuroblastoma Activity of Gold Nanorods Bound with GD2 Monoclonal Antibody under Near-Infrared Laser Irradiation.
abstract: High-risk neuroblastoma is one of the most common deaths in pediatric oncology. Current treatment of this disease involves a coordinated sequence of chemotherapy, surgery, and radiation. Further advances in therapy will require the targeting of tumor cells in a more selective and efficient way so that survival can be improved without substantially increasing toxicity. To achieve tumor-selective delivery, disialoganglioside (GD2) expressed by almost all neuroblastoma tumors represents a potential molecular target that can be exploited for tumor-selective delivery. In this study, GD2 monoclonal antibody (anti-GD2) was conjugated to gold nanorods (GNRs) which are one of anisotropic nanomaterials that can absorb near-infrared (NIR) laser light and convert it to energy for photothermolysis of tumor cells. Thiolated chitosan, due to its biocompatibility, was used to replace cetyltrimethylammonium bromide (CTAB) originally used in the synthesis of gold nanorods. In order to specifically target GD2 overexpressed on the surface of neuroblastoma stNB-V1 cells, anti-GD2 was conjugated to chitosan modified GNRs (CGNRs). To examine the fate of CGNRs conjugated with anti-GD2 after incubation with neuroblastoma cells, rhadoamine B was labeled on CGNRs functionalized with anti-GD2. Our results illustrated that anti-GD2-conjugated CGNRs were extensively endocytosed by GD2+ stNB-V1 neuroblastoma cells via antibody-mediated endocytosis. In addition, we showed that anti-GD2 bound CGNRs were not internalized by GD2- SH-SY5Y neuroblastoma cells. After anti-GD2-linked CGNRs were incubated with neuroblatoma cells for six hours, the treated cells were further irradiated with 808 nm NIR laser. Post-NIR laser exposure, when examined by calcein-AM dye, stNB-V1 cells all underwent necrosis, while non-GD2 expressing SH-SY5Y cells all remained viable. Based on the in vitro study, CGNRs bound with anti-GD2 has the potential to be utilized as a therapeutic thermal coupling agent that generates heat sufficient to selectively kill neuroblastoma cells under NIR laser light exposure.
authors.affiliation: Department of Chemical Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA. cpeng@mtu.edu.
authors.forename: Ching-An
authors.initials: CA
authors.lastname: Peng
authors.forename: Chung-Hao
authors.initials: CH
authors.lastname: Wang