Single Particle and PET-based Platform for Identifying Optimal Plasmonic Nano-Heaters for Photothermal Cancer Therapy

Plasmonic nanoparticle-based photothermal cancer therapy is a promising new tool to inflict localized and irreversible damage to tumor tissue by hyperthermia, without harming surrounding healthy tissue. We developed a single particle and positron emission tomography (PET)-based platform to quantitatively correlate the heat generation of plasmonic nanoparticles with their potential as cancer killing agents. In vitro, the heat generation and absorption cross-section of single irradiated nanoparticles were quantified using a temperature sensitive lipid-based assay and compared to their theoretically predicted photo-absorption. In vivo, the heat generation of irradiated nanoparticles was evaluated in human tumor xenografts in mice using 2-deoxy-2-[F-18]fluoro-D-glucose ((18)F-FDG) PET imaging. To validate the use of this platform, we quantified the photothermal efficiency of near infrared resonant silica-gold nanoshells (AuNSs) and benchmarked this against the heating of colloidal spherical, solid gold nanoparticles (AuNPs). As expected, both in vitro and in vivo the heat generation of the resonant AuNSs performed superior compared to the non-resonant AuNPs. Furthermore, the results showed that PET imaging could be reliably used to monitor early treatment response of photothermal treatment. This multidisciplinary approach provides a much needed platform to benchmark the emerging plethora of novel plasmonic nanoparticles for their potential for photothermal cancer therapy

Plasmonic Bubbles in n-Alkanes

In this paper we study the formation of microbubbles upon the irradiation of an array of plasmonic Au nanoparticles with a laser in n-alkanes ($C_{n}H_{2n+2}$, with n = 5-10). Two different phases in the evolution of the bubbles can be distinguished. In the first phase, which occurs after a delay time {\tau}d of about 100 {\mu}s, an explosive microbubble, reaching a diameter in the range from 10 {\mu}m to 100 {\mu}m, is formed. The exact size of this explosive microbubble barely depends on the carbon chain length of the alkane, but only on the laser power $P_l$. With increasing laser power, the delay time prior to bubble nucleation as well as the size of the microbubble both decrease. In the second phase, which sets in right after the collapse of the explosive microbubble, a new bubble forms and starts growing due to the vaporization of the surrounding liquid, which is highly gas rich. The final bubble size in this second phase strongly depends on the alkane chain length, namely it increases with decreasing number of carbon atoms. Our results have important implications for using plasmonic heating to control chemical reactions in organic solvents

Nanoplasmon-enabled macroscopic thermal management

In numerous applications of energy harvesting via transformation of light into heat the focus recently shifted towards highly absorptive materials featuring nanoplasmons. It is currently established that noble metals-based absorptive plasmonic platforms deliver significant light-capturing capability and can be viewed as super-absorbers of optical radiation. However, direct experimental evidence of plasmon-enabled macroscopic temperature increase that would result from these efficient absorptive properties is scarce. Here we derive a general quantitative method of characterizing light-capturing properties of a given heat-generating absorptive layer by macroscopic thermal imaging. We further monitor macroscopic areas that are homogeneously heated by several degrees with plasmon nanostructures that occupy a mere 8% of the surface, leaving it essentially transparent and evidencing significant heat generation capability of nanoplasmon-enabled light capture. This has a direct bearing to thermophotovoltaics and other applications where thermal management is crucial

Vapor nanobubble is the more reliable photothermal mechanism for inducing endosomal escape of siRNA without disturbing cell homeostasis

Strategies for controlled delivery of therapeutic siRNA into living cells are in high demand as endosomal escape remains the most prominent bottleneck at the intracellular level. Photothermal properties of gold nanoparticles (AuNP) can be used to overcome the endosomal membrane barrier upon laser irradiation by two mechanisms: endosomal rupture by mechanical energy from water vapor nanobubbles (VNBs), or permeabilization of the endosomal membrane by heat diffusion. Here we evaluated how both mechanisms influence cargo release, transfection efficiency, acute cytotoxicity and cell homeostasis. Using a siRNA/AuNP drug delivery system we found that the in vitro release of siRNA from the AuNP carrier occurs equally efficiently by VNB formation or heat generation. Heat-mediated endosomal escape happened more efficiently in cells that had more particles per endosome, resulting in variable siRNA-induced downregulation (20-50%). VNB-mediated endosomal escape did not dependent on the number of AuNP per endosome, yielding high downregulations (50-60%) independent of the cell type. Effects on cell homeostasis by whole transcriptome analysis, showed a quick recover after 24 h or 48 h for either of both photothermal mechanisms. We conclude that VNBs are more consistent to induce efficient endosomal escape and gene silencing independent of the cell type without long lasting effects on cell homeostasis

Nonlinear plasmonics at high temperatures

We solve the Maxwell and heat equations self-consistently for metal nanoparticles under intense continuous wave (CW) illumination. Unlike previous studies, we rely on {\em experimentally}-measured data for the metal permittivity for increasing temperature and for the visible spectral range. We show that the thermal nonlinearity of the metal can lead to substantial deviations from the predictions of the linear model for the temperature and field distribution, and thus, can explain qualitatively the strong nonlinear scattering from such configurations observed experimentally. We also show that the incompleteness of existing data of the temperature dependence of the thermal properties of the system prevents reaching a quantitative agreement between the measured and calculated scattering data. This modelling approach is essential for the identification of the underlying physical mechanism responsible for the thermo-optical nonlinearity of the metal and should be adopted in all applications of high temperature nonlinear plasmonics, especially for refractory metals, both for CW and pulsed illumination