Project description:A hybrid metal-dielectric nano-aperture antenna is proposed for surface-enhanced fluorescence applications. The nano-apertures that formed in the composite thin film consist of silicon and gold layers. These were numerically investigated in detail. The hybrid nano-aperture shows a more uniform field distribution within the apertures and a higher antenna quantum yield than pure gold nano-apertures. The spectral features of the hybrid nano-apertures are independent of the aperture size. This shows a high enhancement effect in the near-infrared region. The nano-apertures with a dielectric gap were then demonstrated theoretically for larger enhancement effects. The hybrid nano-aperture is fully adaptable to large-scale availability and reproducible fabrication. The hybrid antenna will improve the effectiveness of surface-enhanced fluorescence for applications, including sensitive biosensing and fluorescence analysis.
Project description:Metal-enhanced fluorescence of conjugated polyelectrolytes (CPs) is realized using a simple, green hybrid Ag nanocomposite film. Ag nanoparticles (Ag NPs) are pre-prepared by sodium citrate reduction and incorporated into agarose by mixing to form an Ag-containing agarose film (Ag@agarose). Through variation of the amount of Ag NPs in the Ag@agarose film as well as the thickness of the interlayer between CPs and the Ag@agarose film prepared of layer-by-layer assembly of chitosan and sodium alginate, a maximum 8.5-fold increase in the fluorescence of CPs is obtained. After introducing tyrosinase, this system also can be used to detect phenolic compounds with high sensitivity and good visualization under ultraviolet light.
Project description:Amphiphilic biodegradable photoluminescent polymers (ABPLPs) composed of a biodegradable fluorescent polymer and methoxy poly (ethyleneglycol) demonstrate intrinsic bright, tunable, and stable fluorescence emission. ABPLP micelles elicit minor cellular toxicity and can be used for cell and tissue imaging both in vitro and in vivo.
Project description:Nanobubble (NB), which simultaneously enhances ultrasound (US) images and access therapeutic platforms, is required for future cancer treatment. Methods: We designed a theranostic agent for novel cancer treatment by using an NB-encapsulated hybrid nanosystem that can be monitored by US and fluorescent imaging and activated by near-infrared (NIR) light. The nanosystem was transported to the tumor through the enhanced permeability and retention effect. The hybrid nanosystem comprised upconversion nanoparticle (UCNP) and mesoporous silica-coated gold nanorod (AuNR@mS) with the photosensitizer merocyanine 540 to realize dual phototherapy. Results: With the NIR light-triggered, the luminous intensity of the UCNP was enhanced by doping holmium ion and emitted visible green and red lights at 540 and 660 nm. The high optical density state between the UCNP and AuNR@mS can induce plasmonic enhancement to improve the photothermal and photodynamic effects, resulting in cell death by apoptosis. The nanosystem showed excellent stability to avoid the aggregation of nanoparticles during the treatment. JC-1 dye was used as an indicator of mitochondrial membrane potential to identify the mechanism of cell death. The results of in vitro and in vivo analyses confirmed the curative effect of improved dual phototherapy. Conclusion: We developed and showed the therapeutic functions of a novel nanosystem with the combination of multiple theranostic nanoplatforms that can be triggered and activated by 808 nm NIR laser and US.
Project description:PurposeFluorescence molecular imaging, using cancer-targeted near infrared (NIR) fluorescent probes, offers the promise of accurate tumor delineation during surgeries and the detection of cancer specific molecular expression in vivo. However, nonspecific probe accumulation in normal tissue results in poor tumor fluorescence contrast, precluding widespread clinical adoption of novel imaging agents. Here we present the first clinical evidence that fluorescence lifetime (FLT) imaging can provide tumor specificity at the cellular level in patients systemically injected with panitumumab-IRDye800CW, an EGFR-targeted NIR fluorescent probe.Experimental designWe performed wide-field and microscopic FLT imaging of resection specimens from patients injected with panitumumab-IRDye800CW under an FDA directed clinical trial.ResultsWe show that the FLT within EGFR-overexpressing cancer cells is significantly longer than the FLT of normal tissue, providing high sensitivity (>98%) and specificity (>98%) for tumor versus normal tissue classification, despite the presence of significant nonspecific probe accumulation. We further show microscopic evidence that the mean tissue FLT is spatially correlated (r > 0.85) with tumor-specific EGFR expression in tissue and is consistent across multiple patients. These tumor cell-specific FLT changes can be detected through thick biological tissue, allowing highly specific tumor detection and noninvasive monitoring of tumor EFGR expression in vivo.ConclusionsOur data indicate that FLT imaging is a promising approach for enhancing tumor contrast using an antibody-targeted NIR probe with a proven safety profile in humans, suggesting a strong potential for clinical applications in image guided surgery, cancer diagnostics, and staging.
Project description:A detailed study of metal-enhanced fluorescence (MEF) from fluorophores in the blue-to- red spectral region placed in close proximity to thermally evaporated zinc nanostructured films is reported. The zinc nanostructured films were deposited onto glass microscope slides as individual particles and were 1-10 nm in height and 20-100 nm in width, as characterized by Atomic Force Microscopy. The surface plasmon resonance peak of the zinc nanostructured films was approximately 400 nm. Finite-difference time-domain calculations for single and multiple nanostructures organized in a staggered fashion on a solid support predict, as expected, that the electric fields are concentrated both around and between the nanostructures. Additionally, Mie scattering calculations show that the absorption and scattering components of the extinction spectrum are dominant in the UV and visible spectral ranges, respectively. Enhanced fluorescence emission accompanied by no significant changes in excited state lifetimes of fluorophores with emission wavelengths in the visible blue-to-red spectral range near-to zinc nanostructured films were observed, implying that MEF from zinc nanostructured films is mostly due to an electric field enhancement effect.
Project description:We described, for the first time, the metal-enhanced fluorescence from the CdTe nanocrystals spin coated on silver island films (SIFs). CdTe nanocrystals show approximately 5-fold increase in fluorescence intensity, 3-fold decrease in lifetimes, and reduction in blinking on SIF surfaces that can be observed by ensemble and single-molecule fluorescence studies. The single-molecule study also provides further insight on the heterogeneity in the fluorescence enhancement and lifetimes of the CdTe nanocrystals on both glass and SIF surfaces, which is otherwise not possible to observe using ensemble measurements.
Project description:Delivering macromolecules across the skin poses challenges due to the barrier properties of stratum corneum. Different strategies have been reported to cross this barrier, such as chemical penetration enhancers and physical methods like microneedles, sonophoresis, electroporation, laser ablation, etc. Herein, we explored a cationic lipo-polymeric nanocarrier to deliver a model protein across the skin. A cationic amphiphilic lipo-polymer was used to prepare blank nanoplexes, which were subsequently complexed with anionic fluorescein-tagged bovine serum albumin (FITC-BSA). Blank nanoplexes and FITC-BSA complexed nanoplexes showed sizes of 93.72 ± 5.8 (PDI-0.250) and 145.9 ± 3.2 nm (PDI-0.258), respectively, and zeta potentials of 25.6 ± 7.0 mV and 9.17 ± 1.20 mV. In vitro cell culture, and toxicity studies showed optimal use of these nanocarriers, with hemocompatibility data indicating non-toxicity. Ex vivo skin permeation analysis showed a skin permeation rate of 33% after 24 h. The optimized formulation was loaded in a carbopol-based gel that exhibits non-Newtonian flow characteristics with shear-thinning behavior and variable thixotropy. The nanoplexes delivered via gel demonstrated skin permeation of 57% after 24 h in mice skin ex vivo. In vivo skin toxicity testing confirmed the low toxicity profile of these nanocarriers. These results are promising for the transdermal/dermal delivery of macromolecules, such as protein therapeutics, using nanoplexes.
Project description:The last two decades have seen the rise of antimicrobial peptides (AMPs) to combat emerging antibiotic resistance. Herein we report the solid-phase synthesis of short lipidated α/γ-AA hybrid peptides. This family of lipo-chimeric peptidomimetics displays potent and broad-spectrum antimicrobial activity against a range of multi-drug resistant Gram-positive and Gram-negative bacteria. These lipo-α/γ-AA hybrid peptides also demonstrate high biological specificity, with no hemolytic activity towards red blood cells. Fluorescence microscopy suggests that these lipo-α/γ-AA chimeric peptides can mimic the mode of action of AMPs and kill bacterial pathogens via membrane disintegration. As the composition of these chimeric peptides is simple, therapeutic development could be economically feasible and amenable for a variety of antimicrobial applications.
Project description:A thermosensitive polymeric nanoformulation (NF) was fabricated for thermally enhanced near-infrared (NIR) fluorescence imaging (FLI). It comprised core-shell nanoparticles (NPs) with a polystyrene core and a thermosensitive shell of a co-polymer of N-isopropylacrylamide and acrylamide [poly(NIPAM-co-AA)], which underwent a reversible conformational transition at 38-40 °C (corresponding to a lower critical solution temperature, LCST), leading to a reversible shrinkage of NPs from ∼250 nm to ∼140 nm for temperatures above LCST. The NIR dye 3782SL or photosensitizer HPPH were loaded to the NP shells. While the fluorescence of 3782SL and HPPH was quenched in water, it recovered in the NPs dispersion as a result of adsorption by NPs. Fluorescence for 3782SL and HPPH in NF increased when the temperature increased above LCST. Heating of HPPH-loaded NFs led to the elongation of the HPPH fluorescence lifetime and increased the generation of singlet oxygen (1O2). This occurred as a result of the NP shrinkage, corresponding shell compaction and NP aggregation, which hindered the internal conversion for photoexcited molecules adsorbed by NPs, and resulted in an increase in other deactivation pathways, namely fluorescence emission and intersystem crossing. The latter led to an increase in the triplet yield and, consequently, in singlet oxygen generation. Fluorescence microscopy revealed a 2-3-fold increase in the 3782SL or HPPH fluorescence signal from the NF-treated cells after they were heated up to 40 °C. Comparable results were obtained for the FLI of mice in vivo, after subcutaneous, intravenous, or intratumoral NF injections and localized heating by NIR (1.3 μm) laser irradiation. The developed NF holds immense potential for thermally enhanced FLI and photodynamic therapy.