Three-dimensional (3D) plasmonic hot spots for label-free sensing and effective photothermal killing of multiple drug resistant superbugs.

Drug resistant superbug infection is one of the foremost threats to human health. Plasmonic nanoparticles can be used for ultrasensitive bio-imaging and photothermal killing by amplification of electromagnetic fields at nanoscale "hot spots". One of the main challenges to plasmonic imaging and photothermal killing is design of a plasmonic substrate with a large number of "hot spots". Driven by this need, this article reports design of a three-dimensional (3D) plasmonic "hot spot"-based substrate using gold nanoparticle attached hybrid graphene oxide (GO), free from the traditional 2D limitations. Experimental results show that the 3D substrate has capability for highly sensitive label-free sensing and generates high photothermal heat. Reported data using p-aminothiophenol conjugated 3D substrate show that the surface enhanced Raman spectroscopy (SERS) enhancement factor for the 3D "hot spot"-based substrate is more than two orders of magnitude greater than that for the two-dimensional (2D) substrate and five orders of magnitude greater than that for the zero-dimensional (0D) p-aminothiophenol conjugated gold nanoparticle. 3D-Finite-Difference Time-Domain (3D-FDTD) simulation calculations indicate that the SERS enhancement factor can be greater than 104 because of the bent assembly structure in the 3D substrate. Results demonstrate that the 3D-substrate-based SERS can be used for fingerprint identification of several multi-drug resistant superbugs with detection limits of 5 colony forming units per mL. Experimental data show that 785 nm near infrared (NIR) light generates around two times more photothermal heat for the 3D substrate with respect to the 2D substrate, and allows rapid and effective killing of 100% of the multi-drug resistant superbugs within 5 minutes.

Hybrid Theranostic Platform for Second Near-IR Window Light Triggered Selective Two-Photon Imaging and Photothermal Killing of Targeted Melanoma Cells.

Despite advances in the medical field, even in the 21st century cancer is one of the leading causes of death for men and women in the world. Since the second near-infrared (NIR) biological window light between 950 and 1350 nm offers highly efficient tissue penetration, the current article reports the development of hybrid theranostic platform using anti-GD2 antibody attached gold nanoparticle (GNP) conjugated, single-wall carbon nanotube (SWCNT) for second near-IR light triggered selective imaging and efficient photothermal therapy of human melanoma cancer cell. Reported results demonstrate that due to strong plasmon-coupling, two-photon luminescence (TPL) intensity from theranostic GNP attached SWCNT materials is 6 orders of magnitude higher than GNP or SWCNT alone. Experimental and FDTD simulation data indicate that the huge enhancement of TPL intensity is mainly due to strong resonance enhancement coupled with the stronger electric field enhancement. Due to plasmon coupling, the theranostic material serves as a local nanoantennae to enhance the photothermal capability via strong optical energy absorption. Reported data show that theranostic SWCNT can be used for selective two-photon imaging of melanoma UACC903 cell using 1100 nm light. Photothermal killing experiment with 1.0 W/cm(2) 980 nm laser light demonstrates that 100% of melanoma UACC903 cells can be killed using theranostic SWCNT bind melanoma cells after just 8 min of exposure. These results demonstrate that due to plasmon coupling, the theranostic GNP attached SWCNT material serves as a two-photon imaging and photothermal source for cancer cells in biological window II.

Enhancing targeted tumor treatment by near IR light-activatable photodynamic-photothermal synergistic therapy.

For several decades, cancer has been one of the most life-threatening diseases. For enhancing anticancer efficiency with minimum side effects, combination therapy is envisioned. The current manuscript reports for the first time the development of a methylene blue (MB) bound nanoplatform, which is capable of delivering targeted diagnostic and combined synergistic photothermal and photodynamic treatment of cancer. Experimental data found that, once the nanoparticle binds with the target cell surface, it can detect LNCaP human prostate cancer cell selectively using fluorescence imaging. Our result shows that the therapeutic actions can be controlled with external NIR light. No cytotoxicity was observed in the absence of NIR light. Targeted photodynamic and photothermal treatment using 785 nm NIR light indicates that the multimodal treatment enhances the possibility of destroying LNCaP prostate cancer cells in vitro dramatically. We discuss the operating principle for the targeted imaging and possible mechanisms for combined therapeutic actions. Our experimental data show that NIR light activated combined therapy for cancer may become a highly effective treatment procedure in clinical settings.

Theranostic magnetic core-plasmonic shell star shape nanoparticle for the isolation of targeted rare tumor cells from whole blood, fluorescence imaging, and photothermal destruction of cancer.

Cancer is one of the most life-threatening diseases, which causes 7.6 million deaths and around 1 trillion dollars economic loss every year. Theranostic materials are expected to improve early detection and safe treatment through personalized medicine. Driven by the needs, we report the development of a theranostic plasmonic shell-magnetic core star shape nanomaterial based approach for the targeted isolation of rare tumor cells from the whole blood sample, followed by diagnosis and photothermal destruction. Experimental data with whole blood sample spiked with SK-BR-3 cancer cell shows that Cy3 attached S6 aptamer conjugated theranostic plasmonic/magnetic nanoparticles can be used for fluorescence imaging and magnetic separation even in 0.001% mixtures. A targeted photothermal experiment using 1064 nm near-IR light at 2-3 W/cm(2) for 10 min resulted in selective irreparable cellular damage to most of the SK-BR-3 cancer cells. We discuss the possible mechanism and operating principle for the targeted imaging, separation, and photothermal destruction using theranostic magnetic/plasmonic nanotechnology. After the optimization of different parameters, this theranostic nanotechnology-driven assay could have enormous potential for applications as contrast agent and therapeutic actuators for cancer.

A gold nanocage-CNT hybrid for targeted imaging and photothermal destruction of cancer cells.

This communication reports the design of a novel aptamer conjugated gold nanocage decorated SWCNTs hybrid nanomaterial for targeted imaging and selective photothermal destruction of the prostate cancer cells.

Gold nano-popcorn attached SWCNT hybrid nanomaterial for targeted diagnosis and photothermal therapy of human breast cancer cells.

Breast cancer presents greatest challenge in health care in today's world. The key to ultimately successful treatment of breast cancer disease is an early and accurate diagnosis. Current breast cancer treatments are often associated with severe side effects. Driven by the need, we report the design of novel hybrid nanomaterial using gold nano popcorn-attached single wall carbon nanotube for targeted diagnosis and selective photothermal treatment. Targeted SK-BR-3 human breast cancer cell sensing have been performed in 10 cancer cells/mL level, using surface enhanced Raman scattering of single walls carbon nanotube's D and G bands. Our data show that S6 aptamer attached hybrid nanomaterial based SERS assay is highly sensitive to targeted human breast cancer SK-BR-3 cell line and it will be able to distinguish it from other non targeted MDA-MB breast cancer cell line and HaCaT normal skin cell line. Our results also show that 10 min of photothermal therapy treatment by 1.5 W/cm(2) power, 785 nm laser is enough to kill cancer cells very effectively using S6 aptamer attached hybrid nanomaterials. Possible mechanisms for targeted sensing and operating principle for highly efficient photothermal therapy have been discussed. Our experimental results reported here open up a new possibility for using aptamers modified hybrid nanomaterial for reliable diagnosis and targeted therapy of cancer cell lines quickly.

Gold nano-popcorn-based targeted diagnosis, nanotherapy treatment, and in situ monitoring of photothermal therapy response of prostate cancer cells using surface-enhanced Raman spectroscopy.

Prostate cancer is the second leading cause of cancer-related death among the American male population, and the cost of treating prostate cancer patients is about $10 billion/year in the United States. Current treatments are mostly ineffective against advanced-stage prostate cancer and are often associated with severe side effects. Driven by these factors, we report a multifunctional, nanotechnology-driven, gold nano-popcorn-based surface-enhanced Raman scattering (SERS) assay for targeted sensing, nanotherapy treatment, and in situ monitoring of photothermal nanotherapy response during the therapy process. Our experimental data show that, in the presence of LNCaP human prostate cancer cells, multifunctional popcorn-shaped gold nanoparticles form several hot spots and provide a significant enhancement of the Raman signal intensity by several orders of magnitude (2.5 × 10(9)). As a result, it can recognize human prostate cancer cells at the 50-cells level. Our results indicate that the localized heating that occurs during near-infrared irradiation can cause irreparable cellular damage to the prostate cancer cells. Our in situ time-dependent results demonstrate for the first time that, by monitoring SERS intensity changes, one can monitor photothermal nanotherapy response during the therapy process. Possible mechanisms and operating principles of our SERS assay are discussed. Ultimately, this nanotechnology-driven assay could have enormous potential applications in rapid, on-site targeted sensing, nanotherapy treatment, and monitoring of the nanotherapy process, which are critical to providing effective treatment of cancer.