Abstract
Conventional cancer treatment methods suffer from many limitations such as non-specificity in discrimination between healthy and malignant cells. The aim of this study was to investigate the role of polymeric gold-photoactive nanoparticles (PGPNPs) conjugated with folic acid (FA) as theranostic nanoparticles for active targeting, real-time fluorescence tracing and radiosensitivity inducition in LNCaP prostate cancer cells. The cellular uptake and cytotoxicity effect of gold nanoparticles (PGPNPs and PGPNPs-FA) after 2 and 24 h treatment were evaluated in in both cancer (LNCaP) and normal (HUVEC) cells using fluorescent microscopy, Induced coupled plasma optical emission spectrometry (ICP-OES) and Tetrazolium bromide dye (MTT), respectively. The therapeutic efficacy was analyzed on the LNCaP cells. For this purpose, LNCaP cells were treated by nanoparticles and ionizing radiation, and the synergistic effect of treatment methods were evaluated by colony formation assay (CFA) and Flow cytometry analysis. The results of fluorescence imaging and ICP-OES data showed that the LNCaP cells absorbed PGPNP-FA nanoparticles more than PGPNP (P < 0.001). Also, the uptake of nanoparticles was significantly greater in cancer cells than in healthy ones (P < 0.01). MTT assay results indicated higher cytotoxic effect of nanoparticles conjugated with FA in folate-receptor overexpressing LNCaP cancer cells compared to HUVEC normal cells (P < 0.01). Furthermore, CFA and Flow cytometry results demonstrated that combinatorial therapy of polymeric gold nanoparticles with/without FA and ionizing radiation at various doses (2, 4 and 6 Gy) had a synergistic effect on survival fraction and induction of apoptotic and necrotizing cell death (P < 0.01). PGPNPs-FA nanoparticles led to higher and more specific uptake and accumulation of nanoparticles in LNCaP cells, thereby increasing the ability of gold nanoparticles as radio-sensitizer.
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