Push-pull type meso-ester substituted BODIPY near-infrared dyes as contrast agents for photoacoustic imaging.

A series of push-pull type meso-ester substituted BODIPY dyes 1-4 with intense near-infrared absorption, largely enhanced photoacoustic (PA) activity and excellent photo-stability were synthesized. The impact of the electronic structure on the PA activity was also discussed. Moreover, the in vitro and in vivo PA imaging were investigated, which suggested a passive targeting capacity in the tumor site.

Noninvasive in vivo multispectral optoacoustic imaging of apoptosis in triple negative breast cancer using indocyanine green conjugated phosphatidylserine monoclonal antibody.

Noninvasive and nonradioactive imaging modality to track and image apoptosis during chemotherapy of triple negative breast cancer is much needed for an effective treatment plan. Phosphatidylserine (PS) is a biomarker transiently exposed on the outer surface of the cells during apoptosis. Its externalization occurs within a few hours of an apoptotic stimulus by a chemotherapy drug and leads to presentation of millions of phospholipid molecules per apoptotic cell on the cell surface. This makes PS an abundant and accessible target for apoptosis imaging. In the current work, we show that PS monoclonal antibody tagged with indocyanine green (ICG) can help to track and image apoptosis using multispectral optoacoustic tomography

A narrow-bandgap benzobisthiadiazole derivative with high near-infrared photothermal conversion efficiency and robust photostability for cancer therapy.

Photothermal therapy has emerged as a promising tool for treatment of diseases such as cancers. Previous photothermal agents have been largely limited to inorganic nanomaterials and conductive polymers that are barely biodegradable, thus raising issues of long-term toxicity for clinical applications. Here we report a new photothermal agent based on colloidal nanoparticles formed by a small-molecular dye, benzo[1,2-c;4,5-c']bis[1,2,5]thiadiazole-4,7-bis(5-(2-ethylhexyl)thiophene). These nanoparticles showed strong near-infrared absorption, robust photostability and high therapeutic efficiency for photothermal treatment of cancer cells.

Dual functions of gold nanorods as photothermal agent and autofluorescence enhancer to track cell death during plasmonic photothermal therapy.

Gold nanorods have the potential to localize the treatment procedure by hyperthermia and influence the fluorescence. The longitudinal plasmon peak contributes to the photothermal effect by converting light to heat. When these nanorods are PEGylated, it not only makes it biocompatible but also acts as a spacer layer during fluorescence enhancement. When the PEGylated nanorods are internalized inside the cells through endocytosis, the transverse plasmonic peak combined with the enhanced absorption and scattering properties of the nanorods can enhance the autofluorescence emission intensity from the cell. The autofluorescence from the mitochondria inside cells which reflects the respiratory status of the cell was enhanced two times by the presence of nanorods within the cell. At four minutes, the nanorods incubated cells reached the hyperthermic temperature when illuminated continuously with near infrared laser. The cell viability test and autofluorescence intensity curve showed a similar trend indicating the progress of cell death over time. This is the first report to the best of our knowledge to suggest the potential of exploiting the dual capabilities of gold nanorods as photothermal agents and autofluorescence enhancer to track cell death.

Optimization in interstitial plasmonic photothermal therapy for treatment planning.

PURPOSE: Gold nanorods have the potential to enhance the treatment efficacy of interstitial photothermal therapy. In order to enhance both the potential efficiency and the safety of such procedures, treatment planning on laser power density, nanoparticle concentration, and exposure time has turned out to be useful in predicting the thermal damage and optimizing treatment outcome. To the best of our knowledge, there is no previous report on the optimization of interstitial plasmonic photothermal therapy (PPTT) for all these free parameters simultaneously. The authors propose to develop a suitable optimization algorithm for interstitial PPTT to optimize these parameters and achieve complete damage to spherical tumors of different sizes with a damage margin width of 1 mm from the tumor boundary embedded deep inside a normal tissue model. METHODS: In a numerical tissue model, the standard Pennes bioheat equation and the first-order thermal-chemical rate equation were used to model the temperature and thermal damage distributions, respectively, in spherical tumors that were embedded deep inside a normal tissue and incubated with nanorods. The concentration of nanorods in the normal tissue was set to be about one quarter of that in the tumor. Thermal damage due to varying concentrations of nanorods, laser power density, and exposure time was computed for a series of tumor radii including 2, 3, 4, and 5 mm. An optimization algorithm was developed to determine the optimum laser power density, nanorod concentration, and exposure time for the treatment of such spherical tumors. In this algorithm, a novel objective function was created to enable the optimization of multiple key parameters, including nanoparticle concentration, power density, and exposure time, simultaneously to achieve not only the complete thermal damage to the entire tumor but also the collateral damage to the surrounding normal tissue with a margin width of 1 mm from the tumor boundary. Different weights were assigned sequentially to each free parameter according to the relative importance of the parameters. A thermal damage value of one calculated by Arrhenius damage law, which is more accurate than a threshold temperature typically used for characterizing thermal damage, was used to indicate effective treatment. RESULTS: The simulation results show that there is a steady increase in the overall temperature as the nanorod concentration increases; however, the uniformity of the temperature distribution changes significantly which in turn affects the thermal damage. Optimization results show that any slight decrease in one free parameter can be compensated by the increase in other free parameters, in which the complete thermal damage of the tumor and the collateral damage to normal tissue with a margin width of 1 mm can be always achieved. This implies the importance of optimization in interstitial PPTT. CONCLUSIONS: The proposed method can optimize laser power density, nanoparticle concentration, and exposure time simultaneously with different weights in interstitial PPTT planning for deep seated tumors. It provides flexibility for a clinician to make appropriate planning for individual patients according to their special needs.

Fluorescence enhancement using silver nanotriangle arrays.

We describe the fabrication of silver nanotriangle array using angle resolved nanosphere lithography and utilizing the same for enhancing fluorescence. The well established nanosphere lithography is modified by changing the angle of deposition between the nanosphere mask and the beam of silver being deposited resulting in nanotriangles of varying surface area and density. The 470 nm plasmon resonance wavelength of the substrate was determined using minimum reflectivity method which closely matches with excitation wavelength of the fluorophore. Ten times enhancement in fluorescence emission intensity is obtained from fluorescein isothiocyanate coated on top of silver nanotriangle array separated by a spacer layer of poly vinyl alcohol as compared to glass. The enhanced fluorescence emission is attributed to the increase in local field enhancement.

Nanosphere templated metallic grating assisted enhanced fluorescence.

In this paper, enhanced fluorescence from a silver film coated nanosphere templated grating is presented. Initially, numerical simulation was performed to determine the plasmon resonance wavelength by varying the thickness of the silver film on top of a monolayer of 400 nm nanospheres. The simulation results are verified experimentally and tested for enhancing fluorescence from fluorescein isothiocyanate whose excitation wavelength closely matches with the plasmon resonance wavelength of the substrate with 100 nm silver film over nanosphere. The 12 times enhancement in the intensity is attributed to the local field enhancement in addition to the excitation of surface plasmon polaritons along the surface.