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.

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An orthotopic model of papillary thyroid carcinoma was successfully established in nude mice using BRAF-mutated and RET/PTC1-rearranged cell lines. These models mimic the human disease and will thus be useful for evaluating the clinical potential of novel targeted therapies.

Background Patients with pancreatic adenocarcinoma (PDAC) have limited therapeutic options and poor response to the standard gemcitabine (GCB)-based chemotherapy. We investigated the feasibility of non-invasive short-wave RF electric fields to improve cytotoxic effect of GCB on PDAC cells and determined its mechanism of action. Methods Cytotoxicity of RF alone and in combination with GCB was studied in vitro on normal pancreatic HPDE cells and different PDAC cell lines by flow cytometry, and in vivo on ectopic and orthotopic human PDAC xenograft models in mice. Mechanism of RF activity was studied by western blot and immunohistochemistry analysis. Toxicity was determined by histopathology. Results Exposure of different PDAC cells to 13.56 MHz radiowaves resulted in substantial cytotoxic effect, which was accompanied by induction of autophagy, but not apoptosis. These effects of RF were absent in normal cells. Excessive numbers of autophagosomes in cancer cells persisted 24-48 h after RF exposure and then declined. Addition of a subtoxic dose of GCB to RF treatment inhibited the recovery of cancer cells from the RF-induced autophagy and enhanced cytotoxic effect of the latter on cancer cells. Treatment of PDAC cancer in situ in mice with combination of non-invasive RF and GCB had superior antitumor effect than RF or GCB alone, yet had no evidence of systemic toxicity. Conclusions Non-invasive RF treatment induced autophagy, not apoptosis in cancer cells and showed a potential as an enhancer of chemotherapy for treating pancreatic cancer without toxicity to normal cells.

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