Tunable plasmonic nanobubbles for cell theranostics.

Combining diagnostic and therapeutic processes into one (theranostics) and improving their selectivity to the cellular level may offer significant benefits in various research and disease systems and currently is not supported with efficient methods and agents. We have developed a novel method based on the gold nanoparticle-generated transient photothermal vapor nanobubbles, that we refer to as plasmonic nanobubbles (PNB). After delivery and clusterization of the gold nanoparticles (NP) to the target cells the intracellular PNBs were optically generated and controlled through the laser fluence. The PNB action was tuned in individual living cells from non-invasive high-sensitive imaging at lower fluence to disruption of the cellular membrane at higher fluence. We have achieved non-invasive 50-fold amplification of the optical scattering amplitude with the PNBs (relative to that of NPs), selective mechanical and fast damage to specific cells with bigger PNBs, and optical guidance of the damage through the damage-specific signals of the bubbles. Thus the PNBs acted as tunable theranostic agents at the cellular level and in one process that have supported diagnosis, therapy and guidance of the therapy.

Generation and detection of plasmonic nanobubbles in zebrafish.

The zebrafish embryo has been evaluated as an in vivo model for plasmonic nanobubble (PNB) generation and detection at nanoscale. The embryo is easily observed and manipulated utilizing the same methodology as for application of PNBs in vitro. Injection and irradiation of gold nanoparticles with a short laser pulse resulted in generation of PNBs in zebrafish with similar parameters as for PNBs generated in water and cultured living cells. These PNBs do not result in systemic damage, thus we demonstrated an in vivo model for rapid and precise testing of plasmonic nanotechnologies.

Experimental techniques for imaging and measuring transient vapor nanobubbles.

Imaging and measuring transient vapor bubbles at nanoscale pose certain experimental challenges due to their reduced dimensions and lifetimes, especially in a single event experiment. Here, we analyze three techniques that employ optical scattering and acoustic detection in identifying and quantifying individual photothermally induced vapor nanobubbles (NBs) at a wide range of excitation energies. In optically transparent media, the best quantitative detection can be achieved by measuring the duration of the optical scattering time-response, while in an opaque media, the amplitude of the acoustic time-response well describes NBs in the absence of stress waves.