Gold nanoparticles synthesis and functionalization for mitochondrial delivery

TAVERNA PORRO, MARISA L.; GRISSI, CECILIA; ATIA, MARIEL; DURAN, HEBE; IBAÑEZ, IRENE; GARCIA, FRANCISCO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias, LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2017

Melanoma is highly aggressive and its incidence increased significantly over the past decades. Despite the development of improved treatments, patients still have poor prognosis due to its resistance and high recurrence rate. Targeting cancer metabolism has emerged as a promising therapeutic strategy. In this context, multi-resistant melanoma cells have increased mitochondrial respiration and high level of reactive oxygen species. Disruption of this oxidative metabolism, in combination with other conventional therapies, could be an effective means for this highly resistant cancer. However, mitochondrial targeting of therapeutic agents is still challenging. A way to overcome this limitation is by using nanoparticles (NPs). NPs accumulate in tumors by enhanced permeability and retention effect and can be modified for selective mitochondrial targeting. In addition, gold NPs (AuNPs) possess unique electronic properties that make them excellent radiosensitizing agents. Against this background, we propose that AuNPs functionalized with the mitochondriotropic residue triphenylphosphonium (TPP), in combination with radiotherapy, can potentially be used for the radiosensitization of radioresistant melanoma cells. Citrate-AuNPs were prepared by the Turkevich and Frens method and then functionalized with thiolated PEG polymers containing TPP (AuNPs-TPP). AuNPs-TPP were characterized by UV?Vis spectrophotometry, dynamic light scattering and transmission electron microscopy. AuNPs-TPP of 15.7±1.2 nm, highly homogeneous in morphology, with Z potential of 10±0.8 mV and extremely stable were obtained. Stability was demonstrated by no morphology change upon storage time, exposure to high ionic strength and with NPs concentration. AuNPs-TPP up to 250 µg/ml were not cytotoxic in A375 melanoma cells exposed to these NPs for 24 h. All together, these results show that these novel AuNPs functionalized for mitochondrial delivery can potentially be used as radiosensitizers.