Limits...
Anti-Neuroblastoma Activity of Gold Nanorods Bound with GD2 Monoclonal Antibody under Near-Infrared Laser Irradiation.

Peng CA, Wang CH - Cancers (Basel) (2011)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA. cpeng@mtu.edu.

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.

No MeSH data available.


Related in: MedlinePlus

Cell viability of (a) SH-SY5Y and (b) stNB-V1 cells after treatment with different concentrations of GNRs and CGNRs for 24 h as determined by the MTT assay. The bar labels A to D stand respectively for 0.025, 0.05, 0.1, and 0.2 mM (as Au atoms) of twice-centrifuged CGNRs and GNRs in the culture media. Data shown here are the mean ± SD of triplicate experiments.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3756358&req=5

f5-cancers-03-00227: Cell viability of (a) SH-SY5Y and (b) stNB-V1 cells after treatment with different concentrations of GNRs and CGNRs for 24 h as determined by the MTT assay. The bar labels A to D stand respectively for 0.025, 0.05, 0.1, and 0.2 mM (as Au atoms) of twice-centrifuged CGNRs and GNRs in the culture media. Data shown here are the mean ± SD of triplicate experiments.

Mentions: As shown in Figure 5, after stNB-V1 and SH-SY5Y cells were challenged with GNRs and CGNRs concentrations ranging from 0.025 to 0.2 mM for 24 h, cell viability decreased significantly along with the increment of GNR concentration. For example, GNRs with a concentration of 0.1 mM caused viability of SH-SY5Y and stNB-V1 cells to drop to 39% and 36%, respectively. However, these two cell types remained around 90% viable up to the highest CGNR concentration employed for this study. This indicates that decreasing the CTAB concentration in GNR suspension by centrifugation twice would not render GNRs biocompatible. While, thiolated chitosan used to replace CTAB from GNRs could alleviate cytotoxicity to a large extent.


Anti-Neuroblastoma Activity of Gold Nanorods Bound with GD2 Monoclonal Antibody under Near-Infrared Laser Irradiation.

Peng CA, Wang CH - Cancers (Basel) (2011)

Cell viability of (a) SH-SY5Y and (b) stNB-V1 cells after treatment with different concentrations of GNRs and CGNRs for 24 h as determined by the MTT assay. The bar labels A to D stand respectively for 0.025, 0.05, 0.1, and 0.2 mM (as Au atoms) of twice-centrifuged CGNRs and GNRs in the culture media. Data shown here are the mean ± SD of triplicate experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756358&req=5

f5-cancers-03-00227: Cell viability of (a) SH-SY5Y and (b) stNB-V1 cells after treatment with different concentrations of GNRs and CGNRs for 24 h as determined by the MTT assay. The bar labels A to D stand respectively for 0.025, 0.05, 0.1, and 0.2 mM (as Au atoms) of twice-centrifuged CGNRs and GNRs in the culture media. Data shown here are the mean ± SD of triplicate experiments.
Mentions: As shown in Figure 5, after stNB-V1 and SH-SY5Y cells were challenged with GNRs and CGNRs concentrations ranging from 0.025 to 0.2 mM for 24 h, cell viability decreased significantly along with the increment of GNR concentration. For example, GNRs with a concentration of 0.1 mM caused viability of SH-SY5Y and stNB-V1 cells to drop to 39% and 36%, respectively. However, these two cell types remained around 90% viable up to the highest CGNR concentration employed for this study. This indicates that decreasing the CTAB concentration in GNR suspension by centrifugation twice would not render GNRs biocompatible. While, thiolated chitosan used to replace CTAB from GNRs could alleviate cytotoxicity to a large extent.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemical Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931, USA. cpeng@mtu.edu.

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.

No MeSH data available.


Related in: MedlinePlus