Combined treatment of mitochondria-targeted doxycycline conjugated nanoparticles and radiotherapy for resistant melanoma cells

CAMMARATA A.; ATIA M.; GLISONI R.J.; DURAN H.; TAVERNA PORRO M.

Buenos Aires Virtual

Conferencia; 1st Zooming into preclinical Nanomedicines in the era Covid-19; 2020

Asociación Argentina de Nanomedicinas

Cancer stem cells (CSCs) are a subpopulation within tumors, characterized by overexpressing certain mitochondrial proteins. These cells are resistant to conventional chemo and radiotherapies, and can lead to tumor metastasis and recurrence. Nanotechnology allows site-specific and target-oriented delivery of drugs, reducing their side effects. In addition, nanoparticles with high atomic number can be used as radiosensitizers as they can amplify the effect of radiotherapy when exposing cells to radiation. We propose to study the radiosensitizer capacity of gold nanoparticles (AuNPs) conjugated with Doxycycline (DOXY), an inhibitor of mitochondrial biogenesis.We present a nanotechnology strategy for targeting CSCs through inhibition of the mitochondrial function. We also show preliminary results of free DOXY as a radiosensitizer in radioresistant melanoma. Initially, the in vitro effects of DOXY on radiosensitive (A375) and radioresistant (A375-G10 and Mel-J) cell lines were studied. Cell viability and metabolic activity were evaluated by MTT assays. The lines displayed a reduction on cell viability at 25μM of DOXY, being the radioresistant cells more affected. Radiosensitization was studied by clonogenic assays in A375-G10. There was an intensified response to radiation after DOXY treatment.These preliminary results suggest the possibility of controlling radioresistant cells with a mitochondria targeted therapy.