Hypoxia-targeted gold nanorods for cancer photothermal therapy

Abstract

Tumor hypoxia is a well-recognized driver of resistance to traditional cancer therapies such as chemotherapy and radiation therapy. We describe development of a new nanoconstruct composed of gold nanorods (GNRs) conjugated to carbonic anhydrase IX (CAIX) antibody that specifically binds to CAIX, a biomarker of hypoxia, to facilitate targeting tumor hypoxic areas for focused photothermal ablation. Physicochemical characterization studies confirmed the size, shape, monodispersity, surface charge, and serum stability of the GNRs. Enzyme-linked immunosorbent assays and cellular binding and uptake studies confirmed successful conjugation of antibody to the GNRs and specificity for CAIX. Near-infrared irradiation of CAIX-overexpressing cells treated with GNR/anti-CAIX resulted in significantly higher cell death than cells treated with control GNRs. In vivo biodistribution studies using hyperspectral imaging and inductively coupled plasma mass spectrometry confirmed intravenous administration results not only in greater accumulation of GNR/anti-CAIX in tumors than control GNRs but also greater penetration into hypoxic areas of tumors. Near-infrared ablation of these tumors showed no tumor regression in the sham-treated group, regression but recurrence in the non-targeted-GNR group, and complete tumor regression in the targeted-GNR group. GNR/anti-CAIX nanoconstructs show promise as hypoxia targeting and photothermal ablation agents for cancer treatment.

Enhanced Photothermal Treatment Efficacy and Normal Tissue Protection via Vascular Targeted Gold Nanocages

“…Indeed, Ax has been shown to enable vascular targeting of liposomes 22. Other groups have targeted photothermally active materials to epidermal growth factor receptor 23, Her2 24, CD-30 25, carbonic anhydrase IX 26, and even biofilm-forming bacteria 27. These studies demonstrated marked increases in photothermal efficacy relative to their non-targeted analogues.…”

“…The bulk heating effects on the tumor in these situations are ultimately similar to a cauterization or ablative event. Studies that use targeted particles, rather than simply relying on the enhanced permeability and retention effect, have shown improved therapeutic outcomes following photothermal treatment 16, 26, 35, 36.…”

Improvement of Gold Nanorods in Photothermal Therapy: Recent Progress and Perspective

“…Tumor volume plotted over time for all three groups. (D) No tumor regression in the saline-treated group; regression but recurrence of tumor in the GNRs-PEG treated group; and complete tumor regression in the GNRs/anti-CAIX treated group (Chen et al, 2018a). (Hypoxia-targeted gold nanorods for cancer photothermal therapy, https:// creativecommons.org/licenses/by/3.0/).…”

“…Carbonic anhydrase IX (CAIX), a transmembrane protein highly expressed in hypoxic zones, is critically involved in the cellular migration and metastasization of cancer cells. According to Chen et al, GNRs decorated with anti-CAIX antibodies exhibited preferential targeting to hypoxic tumor cells harboring cell-surface CAIX protein, which facilitated the selective ablation of these cells via PTT (Figure 6; Chen et al, 2018b). Interestingly, Fulvio et al found that GNRs showed higher accumulation rates when conjugated with sulfonamides that act as inhibitors toward CAIX than conjugated with anti-CAIX antibodies, inducing the sensitization to subsequent optical ablation (Ratto et al, 2014).…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…Thus, there are some particular groups of NPs such as magnetic nanoparticles , which are usually based in a core of iron oxide mNP with a large magnetic momentum under an external magnetic field, which allow its use as MRI contrast enhancer and thermotherapy agents ( Maier-Hauff et al, 2007 ; van Landeghem et al, 2009 ; Wegscheid et al, 2014 ). Plasmonic nanoparticles refer to mNPs such as gold (Au) or silver (Ag) NPs presenting with surface plasmon resonance (SPR), meaning that NP free electrons can be excited by electromagnetic fields (UV or infrared light) and resonate, creating the possibility to sense these changes (biosensors), produce heat (photothermal ablation/therapy), or create technologies such as surface-enhanced Raman spectroscopy (SERS) ( Kaur et al, 2016 ; Chen et al, 2018 ; Liu et al, 2018 ). Quantum dots (Qdots) are another group of inorganic NPs, usually smaller than 50 nm; these semiconductor NPs efficiently produce bioluminescence once excited by UV light, which has led them to be used in single cell and in vivo imaging ( Xu et al, 2006 ; Figure 1 ).…”