Control of pore structure in a porous gold nanoparticle for effective cancer cell damage.

For tumor treatment, compared with gold nanoparticles (NPs) of other geometries, a porous gold NP (PGNP) has the advantages of stronger localized surface plasmon resonance (LSPR) due to the pore nanostructures and a larger surface area to link with more drug or photosensitizer (PS) molecules for more effective delivery into cancer cells. Different from the chemical synthesis methods, in this paper we demonstrate the fabrication procedures of PGNP based on shaped Au/Ag deposition on a Si substrate and elucidate the advantageous features. PGNPs fabricated under different conditions, including different deposited Au/Ag content ratios and different alloying annealing temperatures, are compared for optimizing the fabrication condition in terms of LSPR wavelength, PS linkage capability, and cancer cell damage efficiency. It is found that within the feasible fabrication parameter ranges, the Au/Ag content ratio of 3:7 and alloying annealing temperature at 600 °C are the optimized conditions. In comparing with widely used gold NPs of other geometries, PGNP fabricated under the optimized conditions can be used for achieving a significantly higher linked PS molecule number per unit gold weight.

Enhancements of Cancer Cell Damage Efficiencies in Photothermal and Photodynamic Processes through Cell Perforation and Preheating with Surface Plasmon Resonance of Gold Nanoring.

The methods of cell perforation and preheating are used for increasing cell uptake efficiencies of gold nanorings (NRIs), which have the localized surface plasmon resonance wavelength around 1064 nm, and photosensitizer, AlPcS, and hence enhancing the cell damage efficiency through the photothermal (PT) and photodynamic (PD) effects. The perforation and preheating effects are generated by illuminating a defocused 1064-nm femtosecond (fs) laser and a defocused 1064-nm continuous (cw) laser, respectively. Cell damage is produced by illuminating cell samples with a focused 1064-nm cw laser through the PT effect, a focused 1064-nm fs laser through both PT and PD effects, and a focused 660-nm cw laser through the PD effect. Under various conditions with and without cell wash before laser illumination, through either perforation or preheating process, cell uptake and hence cell damage efficiencies can be enhanced. Under our experimental conditions, perforation can be more effective at enhancing cell uptake and damage when compared with preheating.

Exocytosis of gold nanoparticle and photosensitizer from cancer cells and their effects on photodynamic and photothermal processes.

We first illustrate the faster decrease of the photothermal (PT) effect with the delay time of laser treatment, in which the illumination of a 1064 nm laser effectively excites the localized surface plasmon (LSP) resonance of cell-up-taken gold nanoring (NRI) linked with a photosensitizer (PS), when compared with the photodynamic (PD) effect produced by the illumination of a 660 nm laser for effective PS excitation. The measurement results of the metal contents of Au NRI and PS based on inductively coupled plasma mass spectroscopy and the PS fluorescence intensity based on flow cytometry show that the linkage of NRI and PS is rapidly broken for releasing PS through the effect of glutathione in lysosome after cell uptake. Meanwhile, NRI escapes from a cell with a high rate such that the PT effect decays fast while the released PS can stay inside a cell longer for producing a prolonged PD effect. The effective delivery of PS through the linkage with Au NRI for cell uptake and the advantageous effect of LSP resonance at a PS absorption wavelength on the PD process are also demonstrated.

Cancer cell death pathways caused by photothermal and photodynamic effects through gold nanoring induced surface plasmon resonance.

The different death pathways of cancer cells under the conditions of the photothermal (PT), effect, photodynamic (PD) effect, and their combination are evaluated. By incubating cells with Au nanoring (NRI) either linked with the photosensitizer, AlPcS, or not, the illumination of a visible continuous laser for exciting the photosensitizer or an infrared femtosecond laser for exciting the localized surface plasmon resonance of Au NRI, leads to various PT and PD conditions for study. Three different staining dyes are used for identifying the cell areas of different damage conditions at different temporal points of observation. The cell death pathways and apoptotic evolution speeds under different cell treatment conditions are evaluated based on the calibration of the threshold laser fluences for causing early-apoptosis (EA) and necrosis (NE) or late-apoptosis (LA). It is found that with the PT effect only, strong cell NE is generated and the transition from EA into LA is faster than that caused by the PD effect when the EA stage is reached within 0.5 h after laser illumination. By combining the PT and PD effects, in the first few hours, the transition speed becomes lower, compared to the case of the PT effect only, when both Au NRIs internalized into cells and adsorbed on cell membrane exist. When the Au NRIs on cell membrane is removed, in the first few hours, the transition speed becomes higher, compared to the case of the PD effect only.