COX-2 gene silencing by laser-assisted oligonucleotides release from remote optical Nano-switches (LORONS) in hepatocellular carcinoma cells.

[BACKGROUND] Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocellular carcinoma (HCC). Selective inhibition of COX-2 can come forward as improved and targeted therapeutic strategy.

[METHODS] We hereby determine selective inhibition efficiency of COX-2 enzyme in HepG cells through laser-assisted oligonucleotides release from remote optical nano-switches (LORONS) with spatial and temporal control. Gold nanorods (GNRs) were decorated with fluorescein labeled single and double strand RNA interfering oligos through methoxy PEG thiol linkages. Upon uptake by HepG cell, conjugated GNRs were exposed to continuous NIR laser irradiation near the resonance wavelength of GNRs (808 nm) for controlled release of oligos.

[RESULTS] COX-2 protein expression was reduced by 93% after NIR laser exposure compared to control sample after 48 h ( < 0.05). Significant reduction in prostaglandin E2(PGE2) levels after LORONS treatment was also observed. Gene silencing efficacy using GNRs conjugated oligos without laser exposure was recorded 38%.

[CONCLUSION] We hereby conclude LORONS as a useful therapeutic strategy for localized gene silencing by remote optical excitation at desired intracellular location.