The Synergistic Cytotoxic Effect of Laser-Irradiated Gold Nanoparticles and Sorafenib Against the Growth of a Human Hepatocellular Carcinoma Cell Line.

Gold nanoparticles are the most promising candidate in cancer treatment due to their physiochemical properties
and increased use in photothermal therapy (PTT). In the present study, spherical gold nanoparticles (AuNPs) were
synthesized using citrate reduction method. The particles were then characterized using UV-VIS spectroscopy and
transmission electron microscope. A hepatocellular carcinoma cell line (HepG2) was incubated with sorafenib and/or
non-irradiated or laser-irradiated AuNPs for 48 hrs. The cytotoxic effect of different treatment modalities was determined
using MTT assay. Furthermore, apoptosis was determined by flow cytometry using annexin V/propidium iodide, as
well as estimating the level of caspases. Results showed that AuNPs and sorafenib reduced HepG2 cell viability, and
the cytotoxicity was associated with increased release of LDH in the culture medium. The recorded cytotoxicity was
attributed to enhanced apoptosis as revealed by increased cellular caspases (3, 8 and 9), that was further confirmed by
flow cytometry. The most notable cytotoxic effect was recorded when combining sorafenib with laser-irradiated AuNPs.
In conclusion, a synergistic cytotoxic effect was observed between sorafenib and laser-irradiated AuNPs against the
growth of HepG2, suggesting the potential substitution of large toxic doses of sorafenib by lower doses in combination
with photothermal therapy.

Photodecomposition, photomutagenicity and photocytotoxicity of retinyl palmitate under He-Ne laser photoirradiation and its effects on photodynamic therapy of cancer cells in vitro.

OBJECTIVE: Our aim was to study photodecomposition, photomutagenicity and cytotoxicity of retinyl palmitate (RP), a principal storage form of vitamin A in humans and animals, under He-Ne laser photoirradiation. Moreover, the effect of different concentrations and timing protocol of antioxidants on photodynamic therapy (PDT) is contradictory, so the effect of RP (as antioxidant) on the PDT cytotoxicity was studied. METHODS: Photomutagenicity was tested by Ames test. Photodecomposition was studied by UV-vis spectroscopy. Cytotoxicity was measured with MTT-assay. Moreover, the effect of PDT, using hematoporphyrin derivatives (HpD) as photosensitizer under He-Ne laser irradiation (10 J/cm(2)), was studied on HeLa cells either with or without RP (1-100 µM) which incubated with the cells for short or long incubation period (1 h or 24 h) prior to PDT. RESULTS: No photodecomposition of RP alone was obseved whereas there is a little photodecomposition of RP only in presence of HpD under irradiation with He-Ne laser. Moreover, no photomutagenicity was observed in Salmonella typhimurium strains under laser irradiation in presence or absence of HpD. RP alone (1-100 µM) significantly decrease the viability of HeLa cells. Laser irradiation of HeLa cells pre-incubated with RP alone for 24 h showed further significant decrease in viability of the cells. While RP incubations for 1 h before PDT had slight effect on the cells, 24 h incubation before PDT enhanced the cytotoxicity of PDT on HeLa cells. CONCLUSIONS: RP can be used 24 h before PDT to enhance its effects. RP is not mutagenic under irradiation with He-Ne laser.