Multiscale modeling of plasmonic enhanced energy transfer and cavitation around laser-excited nanoparticles.

Nanoscale bubbles generated around laser-excited metallic nanoparticles are promising candidates for targeted drug and gene delivery in living cells. The development of new nanomaterials for efficient nanobubble-based therapy is however limited by the lack of reliable computational approaches for the prediction of their size and dynamics, due to the wide range of time and space scales involved. In this work, we present a multiscale modeling framework that segregates the various channels of plasmon de-excitation and energy transfer to describe the generation and dynamics of plasmonic nanobubbles. Detailed comparison with time-resolved shadowgraph imaging and spectroscopy data demonstrates that the bubble size, dynamics, and formation threshold can be quantitatively predicted for various types of nanostructures and irradiation parameters, with an error smaller than the experimental uncertainty. Our model in addition provides crucial physical insights into non-linear interactions in the near-field that should guide the experimental design of nanoplasmonic materials for nanobubble-based applications in nanomedicine.

Rational Design of Plasmonic Nanoparticles for Enhanced Cavitation and Cell Perforation.

Metallic nanoparticles are routinely used as nanoscale antenna capable of absorbing and converting photon energy with subwavelength resolution. Many applications, notably in nanomedicine and nanobiotechnology, benefit from the enhanced optical properties of these materials, which can be exploited to image, damage, or destroy targeted cells and subcellular structures with unprecedented precision. Modern inorganic chemistry enables the synthesis of a large library of nanoparticles with an increasing variety of shapes, composition, and optical characteristic. However, identifying and tailoring nanoparticles morphology to specific applications remains challenging and limits the development of efficient nanoplasmonic technologies. In this work, we report a strategy for the rational design of gold plasmonic nanoshells (AuNS) for the efficient ultrafast laser-based nanoscale bubble generation and cell membrane perforation, which constitute one of the most crucial challenges toward the development of effective gene therapy treatments. We design an in silico rational design framework that we use to tune AuNS morphology to simultaneously optimize for the reduction of the cavitation threshold while preserving the particle structural integrity. Our optimization procedure yields optimal AuNS that are slightly detuned compared to their plasmonic resonance conditions with an optical breakdown threshold 30% lower than randomly selected AuNS and 13% lower compared to similarly optimized gold nanoparticles (AuNP). This design strategy is validated using time-resolved bubble spectroscopy, shadowgraphy imaging and electron microscopy that confirm the particle structural integrity and a reduction of 51% of the cavitation threshold relative to optimal AuNP. Rationally designed AuNS are finally used to perforate cancer cells with an efficiency of 61%, using 33% less energy compared to AuNP, which demonstrate that our rational design framework is readily transferable to a cell environment. The methodology developed here thus provides a general strategy for the systematic design of nanoparticles for nanomedical applications and should be broadly applicable to bioimaging and cell nanosurgery.

Plasma mediated off-resonance plasmonic enhanced ultrafast laser-induced nanocavitation.

The generation of nanobubbles around plasmonic nanostructures is an efficient approach for imaging and therapy, especially in the field of cancer research. We show a novel method using infrared femtosecond laser that generates ≈800 nm bubbles around off-resonance gold nanospheres using 200 mJ/cm(2) 45 fs pulses. We present experimental and theoretical work that demonstrate that the nanobubble formation results from the generation of a nanoscale plasma around the particle due to the enhanced near-field rather than from the heating of the particle. Energy absorbed in the nanoplasma is indeed more than 11 times the energy absorbed in the particle. When compared to the usual approach that uses nanosecond laser to induce the extreme heating of in-resonance nanoparticles to initiate bubble formation, our off-resonance femtosecond technique is shown to bring many advantages, including avoiding the particles fragmentation, working in the optical window of biological material and using the deposited energy more efficiently.

Off-resonance plasmonic enhanced femtosecond laser optoporation and transfection of cancer cells.

A femtosecond laser based transfection method using off-resonance plasmonic gold nanoparticles is described. For human cancer melanoma cells, the treatment leads to a very high perforation rate of 70%, transfection efficiency three times higher than for conventional lipofection, and very low toxicity (<1%). Off-resonance laser excitation inhibited the fracture of the nanoparticles into possibly toxic DNA intercalating particles. This efficient and low toxicity method is a promising alternative to viral transfection for skin cancer treatment.