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Aziliz Hervault

UCL Healthcare Biomagnetic Labs

Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally and the possibility to benefit from the synergistic effect of the combined therapy. Bioluminescence imaging is an optical imaging technique that is based on the sensitive detection of photons emitted during the bioluminescence reaction from bioreporter cells expressing Luciferase. A novel magnetic nanocomposite composed of a superparamagnetic iron oxide core and a pH- and thermo-responsive polymer shell that can be used as both mediators of heat and drug carriers for the treatment of cancer was previously developed. The dual stimuli-responsive behaviour provides advanced features offering spatial and temporal control over the release of the anti-cancer drug doxorubicin in response to magnetic hyperthermia and tumour acidic pH, therefore limiting unwanted side effects. In vitro experiments performed on a murine prostate carcinoma RM1 cell line genetically modified to express the enzyme Firefly Luciferase confirmed that thermo-chemotherapy treatment applied via the developed smart delivery system exhibits a substantial increase in cytotoxicity as compared to chemotherapy or magnetic hyperthermia as standalone therapies. Cell viabilities were determined by monitoring Luciferase activity using the bioluminescence imaging method. For a treatment applied after internalisation of the nanoparticles inside the cells and subsequent washing, the relative cell viabilities 24 h post-treatment are 65 % for hyperthermia, 82 % for chemotherapy and 44 % for thermo-chemotherapy. For direct treatment which consists in subjecting the cells to an alternating magnetic field directly after mixing them with the nanoparticles, the relative cell viabilities 24 h post-treatment are 93 % for chemotherapy, 89 % for hyperthermia and 57 % for thermo-chemotherapy at 42 °C, 70 % for hyperthermia and 26 % for thermo-chemotherapy at 43 °C. In each case, the combined effects were found to be synergistic in nature.