Integrated molecular targeting of IGF1R and HER2 surface receptors and destruction of breast cancer cells using single wall carbon nanotubes

Abstract

Molecular targeting and photodynamic therapy have shown great potential for selective cancer therapy. We hypothesized that monoclonal antibodies that are specific to the IGF1 receptor and HER2 cell surface antigens could be bound to single wall carbon nanotubes (SWCNT) in order to concentrate SWCNT on breast cancer cells for specific near-infrared phototherapy. SWCNT functionalized with HER2 and IGF1R specific antibodies showed selective attachment to breast cancer cells compared to SWCNT functionalized with non-specific antibodies. After the complexes were attached to specific cancer cells, SWCNT were excited by ∼808 nm infrared photons at ∼800 mW cm−2 for 3 min. Viability after phototherapy was determined by Trypan blue exclusion. Cells incubated with SWCNT/non-specific antibody hybrids were still alive after photo-thermal treatment due to the lack of SWNT binding to the cell membrane. All cancerous cells treated with IGF1R and HER2 specific antibody/SWCNT hybrids and receiving infrared photons showed cell death after the laser excitation. Quantitative analysis demonstrated that all the cells treated with SWCNT/IGF1R and HER2 specific antibody complex were completely destroyed, while more than 80% of the cells with SWCNT/non-specific antibody hybrids remained alive. Following multi-component targeting of IGF1R and HER2 surface receptors, integrated photo-thermal therapy in breast cancer cells led to the complete destruction of cancer cells. Functionalizing SWCNT with antibodies in combination with their intrinsic optical properties can therefore lead to a new class of molecular delivery and cancer therapeutic systems.

Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

“…A tumor targeted NDDS generally combines tumor-recognition moiety with drug-loaded nanoparticles. [7][8][9][10][11][12][13] In recent years, various nanosized drug-delivery vehicles have been evaluated, [14][15][16] of which carbon nanotubes (CNTs) 17,18 have been shown to be advantageous to cancer therapy and imaging. Single-walled CNTs (SWCNTs), which are thin sheets of benzene rings rolled up into the shape of seamless cylinders with many unique physical and chemical properties, have attracted significant attention as promising drug-delivery nanovehicles for cancer diagnosis and chemotherapy, due to such advantages as remarkable cell-membrane penetrability, high drug-loading capacity, pH-dependent therapeutic unloading, and prolonged circulation half-lives.…”

“…17,18,29,47,48 The intrinsic properties of SWCNTs are suitable for these techniques due to their strong optical absorbance in the NIR region, which can release significant heat and enhance the thermal destruction of cells during NIR laser irradiation.…”

Current applications and future prospects of nanomaterials in tumor therapy

“…Kam et al 104 showed that this approach is effective. In a similar work, 105 the authors showed that HER2-IGFR-SWCNTs were able to destroy all targeted tumor cells. MWCNTs also efficiently absorb NIR light and efficiently convert the absorbed energy into thermal energy.…”

Carbon nanotubes as a novel drug delivery system for anticancer therapy: a review

“…Moreover, SWCNTs have been shown to enter mammalian cells Chin et al, 2007;Kam et al, 2004;Kostarelos et al, 2007) and due to their promising properties, SWCNT-based materials have already been investigated as potential delivery vehicles for intracellular transport of nucleic acids Pantarotto et al, 2004), proteins (Kam et al, 2004; and drug molecules Chen et al, 2008;. SWCNTs have been functionalized with antibodies and low-molecular-weight targeting agents, providing high efficiency for nanotube internalization into cells Bottini et al, 2006;Cato et al, 2008, Singh et al, 2005Kang et al, 2008;Shao et al, 2007;Welsher et al, 2008;Zeineldin et al, 2009).These systems also have higher loading capacity and allow for the incorporation of targeting agents and stealth molecules may also be added to evade the immune system. (Mu et al, 2009;Heister et al,2009) Such systems have been loaded with drug molecules such as doxorubicin (DOX) via p-p stacking interactions, methotrexate, Paclitaxel and quercetin.…”