Stability of antibody-conjugated gold nanoparticles in the endolysosomal nanoenvironment: implications for noninvasive radiofrequency-based cancer therapy

Abstract

The use of non-invasive radiofrequency (RF) electric fields as an energy source for thermal activation of nanoparticles within cancer cells could be a valuable addition to the emerging field of nano-mediated cancer therapies. Based on investigations of cell death through hyperthermia, and offering the ability for total body penetration by RF fields, this technique is thought to compliment and possibly out-perform existing nano-heat-treatments that utilize alternative heat production via optical or magnetic stimuli. However, it remains a challenge to understand fully the complex RF-nanoparticle-intracellular interactions before full system optimization can be engineered. Herein we have shown that liver cancer cells can selectively internalize antibody-conjugated gold nanoparticles (AuNPs) through receptor-mediated endocytosis, with the nanoparticles predominantly accumulating and aggregating within cytoplasmic endo-lysosomes. After exposure to an external RF field, non-aggregated AuNPs absorbed and dissipated energy as heat causing thermal damage to the targeted cancer cells. We also observed that RF absorption and heat dissipation is dependent on solubility of AuNPs in the colloid, which is pH dependent. Furthermore, by modulating endo-lysosomal pH it is possible to prevent intracellular AuNP aggregation and enhance thermal cytotoxicity in hepatocellular cancer cells.

Protein corona modulation of hepatocyte uptake and molecular mechanisms of gold nanoparticle toxicity

“…Maintenance medium served as a dispersant. Dose selection was based on concentration ranges for thermal therapy in vitro which used 0.1 mg/mL of Au nanospheres in human hepatocarcinoma cells SNU0-449 (Raoof et al, 2012), 0.05-0.5 mg/mL of Au nanoshelled microcapsules in HeLa cells (Ke et al, 2011) and 4 nM of citrate-Au nanospheres in HepG2 (Cardinal et al, 2008). After 24 h, the cell culture was incubated with alamarBlue V R (Thermo Scientific, Waltham, MA) diluted in maintenance medium (1:1, v/v).…”

Water-structuring molecules and nanomaterials enhance radiofrequency heating in biologically relevant solutions

“…It was hypothesized that AuNPs functionalized with cancer targeting surface moieties would allow for high intratumoral accumulation and therefore localized heating due to their metallic, electronic properties. This has been met with some success both in vitro and in vivo 10–11 but has been the subject of intense debate in regards to the origins of heat production.…”

Tumor-specific hyperthermia with aptamer-tagged superparamagnetic nanoparticles

“…Hyperthermia provided by AuNPs was evaluated by Raoof et al 25 The particles were conjugated with an antibody against EGFR via an Au-S interaction. The bioconjugate was internalized by EGFR-overexpressing cells, which were then subjected to radiofrequency.…”