Iron oxide@chlorophyll clustered nanoparticles eliminate bladder cancer by photodynamic immunotherapy-initiated ferroptosis and immunostimulation.

The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe3O4 and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe3O4@Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower "off" signal to the effector immune cells), IDO-1, TGF-ß, and M2-like macrophages and the induction of CD8+ T cells on BC sections. Moreover, the intravesical instillation of Fe3O4@Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.

Predictive factors for disease recurrence in patients with locally advanced renal cell carcinoma treated with curative surgery.

BACKGROUND: Few prognostic factors have been proposed for patients with locally advanced renal cell carcinoma (RCC). This study aimed to investigate the possible predictive factors for disease-free survival (DFS) after curative surgery for RCC stage T3 or higher. METHODS: Patients with locally advanced RCC who underwent cure-intended partial or radical nephrectomy, with or without tumor thrombectomy, at our institution from April 1, 2005 to October 31, 2013 were retrospectively reviewed. Those undergoing cytoreductive nephrectomy were excluded. Preoperative data, including surgical and pathologic characteristics, were assessed for correlation with DFS. Chi-square tests, univariate and multivariate Cox regression analysis, and Kaplan-Meier survival curve analyses were performed to determine potential predictive factors. A p value less than 0.05 was considered statistically significant. RESULTS: A total of 159 patients were included for analysis. The mean duration of follow-up was 37.9 months, and 119 (74.8%) patients remained disease-free during follow-up. Disease recurrence was found in 40 (25.2%) patients, and pathologic T stage, capsule penetration, Fuhrman grade, thrombocytosis, renal vein thrombosis, and elevated serum alkaline phosphatase, platelet/lymphocyte ratio, and γ-glutamyl transpeptidase levels were significantly associated with disease recurrence on univariate analysis. On multivariate analysis, Fuhrman grade 3 or 4 (HR = 5.70, p = 0.0003, 95% CI = 2.23-14.56) showed significant associations with DFS. CONCLUSION: In patients with locally advanced RCC, Fuhrman grade was associated with worse DFS after curative surgery. Urologists should closely monitor patients with high Fuhrman grades.

Optical manipulation of nematic colloids at the interfaces in azo-dye-doped liquid crystals.

This study demonstrates the optical manipulation of colloids dispersed in azo-dye-doped liquid crystals (DDLCs) where the accumulation occurs at the interfaces of the phase domains. We explain the mechanism related to the formation of the domains and the movement of the colloids in DDLCs with respect to the isomerization of azo-dye molecules via the illumination of laser beams. The colloids are dragged to the interfaces of the isotropic/nematic domain and the air bubble/isotropic domain by molecular interaction and Marangoni flows.

3D Plasmon Coupling Assisted Sers on Nanoparticle-Nanocup Array Hybrids.

Unique colorimetric optical properties of nanomaterials can effectively influence the light absorption or emission of molecules. Here, we design plasmonic substrate for surface-enhanced Raman scattering (SERS) by inducing three-dimensional (3D) hot spots on the sensing surface. The 3D hot spots are formed by the self-assembly of plasmonic nanoparticles (NPs) on a 3D plasmonic nanocup array structure. This 3D hot spot formation on the periodic nanocup arrays achieves much higher SERS enhancement factor than the 2D NP arrays, which have been conventionally sought SERS substrates. We also utilize the colorimetric properties of the nanocup arrays for an additional degree of SERS enhancement. Colorimetry, achieved by tunable plasmon resonance wavelength by controlling dielectric property on the nanocup array surface, eases the modulation of the plasmonic resonance condition without modifying the nanostructure design. By continuously monitoring the shifts of the plasmon resonance condition and its effect on the light absorption and emission of the nearby molecules, we verify that larger SERS enhancement is achieved when the plasmon resonance wavelength is matched with the Raman excitation wavelength. The ease of plasmon resonance tuning of this nanocup array-nanoparticle hybrid structure allows versatile SERS enhancement for a variety of different Raman measurement conditions.

Plasmonic nanohole array for enhancing the SERS signal of a single layer of graphene in water.

We numerically design and experimentally test a SERS-active substrate for enhancing the SERS signal of a single layer of graphene (SLG) in water. The SLG is placed on top of an array of silver-covered nanoholes in a polymer and is covered with water. Here we report a large enhancement of up to 2 × 105 in the SERS signal of the SLG on the patterned plasmonic nanostructure for a 532 nm excitation laser wavelength. We provide a detailed study of the light-graphene interactions by investigating the optical absorption in the SLG, the density of optical states at the location of the SLG, and the extraction efficiency of the SERS signal of the SLG. Our numerical calculations of both the excitation field and the emission rate enhancements support the experimental results. We find that the enhancement is due to the increase in the confinement of electromagnetic fields on the location of the SLG that results in enhanced light absorption in the graphene at the excitation wavelength. We also find that water droplets increase the density of optical radiative states at the location of the SLG, leading to enhanced spontaneous emission rate of graphene at its Raman emission wavelengths.

Marangoni Convection Assisted Single Molecule Detection with Nanojet Surface Enhanced Raman Spectroscopy.

Many single-molecule (SM) label-free techniques such as scanning probe microscopies (SPM) and magnetic force spectroscopies (MFS) provide high resolution surface topography information, but lack chemical information. Typical surface enhanced Raman spectroscopy (SERS) systems provide chemical information on the analytes, but lack spatial resolution. In addition, a challenge in SERS sensors is to bring analytes into the so-called "hot spots" (locations where the enhancement of electromagnetic field amplitude is larger than 103). Previously described methods of fluid transport around hot spots like thermophoresis, thermodiffusion/Soret effect, and electrothermoplasmonic flow are either too weak or detrimental in bringing new molecules to hot spots. Herein, we combined the resonant plasmonic enhancement and photonic nanojet enhancemnet of local electric field on nonplanar SERS structures, to construct a stable, high-resolution, and below diffraction limit platform for single molecule label-free detection. In addition, we utilize Marangoni convection (mass transfer due to surface tension gradient) to bring new analytes into the hotspot. An enhancement factor of ∼3.6 × 1010 was obtained in the proposed system. Rhodamine-6G (R6G) detection of up to a concentration of 10-12 M, an improvement of two orders of magnitude, was achieved using the nanojet effect. The proposed system could provide a simple, high throughput SERS system for single molecule analysis at high spatial resolution.

Self-Referenced Smartphone-Based Nanoplasmonic Imaging Platform for Colorimetric Biochemical Sensing.

Colorimetric sensors usually suffer due to errors from variation in light source intensity, the type of light source, the Bayer filter algorithm, and the sensitivity of the camera to incoming light. Here, we demonstrate a self-referenced portable smartphone-based plasmonic sensing platform integrated with an internal reference sample along with an image processing method to perform colorimetric sensing. Two sensing principles based on unique nanoplasmonics enabled phenomena from a nanostructured plasmonic sensor, named as nanoLCA (nano Lycurgus cup array), were demonstrated here for colorimetric biochemical sensing: liquid refractive index sensing and optical absorbance enhancement sensing. Refractive indices of colorless liquids were measured by simple smartphone imaging and color analysis. Optical absorbance enhancement in the colorimetric biochemical assay was achieved by matching the plasmon resonance wavelength with the chromophore's absorbance peak wavelength. Such a sensing mechanism improved the limit of detection (LoD) by 100 times in a microplate reader format. Compared with a traditional colorimetric assay such as urine testing strips, a smartphone plasmon enhanced colorimetric sensing system provided 30 times improvement in the LoD. The platform was applied for simulated urine testing to precisely identify the samples with higher protein concentration, which showed potential point-of-care and early detection of kidney disease with the smartphone plasmonic resonance sensing system.

Large-area, uniform and low-cost dual-mode plasmonic naked-eye colorimetry and SERS sensor with handheld Raman spectrometer.

We demonstrated a highly-sensitive, wafer-scale, highly-uniform plasmonic nano-mushroom substrate based on plastic for naked-eye plasmonic colorimetry and surface-enhanced Raman spectroscopy (SERS). We gave it the name FlexBrite. The dual-mode functionality of FlexBrite allows for label-free qualitative analysis by SERS with an enhancement factor (EF) of 10(8) and label-free quantitative analysis by naked-eye colorimetry with a sensitivity of 611 nm RIU(-1). The SERS EF of FlexBrite in the wet state was found to be 4.81 × 10(8), 7 times stronger than in the dry state, making FlexBrite suitable for aqueous environments such as microfluid systems. The label-free detection of biotin-streptavidin interaction by both SERS and colorimetry was demonstrated with FlexBrite. The detection of trace amounts of the narcotic drug methamphetamine in drinking water by SERS was implemented with a handheld Raman spectrometer and FlexBrite. This plastic-based dual-mode nano-mushroom substrate has the potential to be used as a sensing platform for easy and fast analysis in chemical and biological assays.

Substrate binding to cytochrome P450-2J2 in Nanodiscs detected by nanoplasmonic Lycurgus cup arrays.

Cytochrome P450s are the primary enzymes involved in phase I drug metabolism. They are an important target for early drug discovery research. However, high-throughput drug screening of P450s is limited by poor protein stability and lack of consistent measurement of binding events. Here we present the detection of substrate binding to cytochrome P450-2J2 (CYP2J2), the predominant P450 in the human heart, using a combination of Nanodisc technology and a nanohole plasmonic sensor called nanoplasmonic Lycurgus cup array (nanoLCA). The Nanodisc, a nanoscale membrane bilayer disc, is used to stabilize the protein on the metallic plasmonic surface. Absorption spectroscopy of seven different substrates binding to CYP2J2 in solution showed that they are all type I, resulting in shifting of the protein bands to lower wavelengths (blue shift). Detection on the nanoLCA sensor also showed spectral blue shifts of CYP2J2 following substrate binding. Finite Difference Time Domain (FDTD) electromagnetic simulation suggested that the blue shift on the nanoLCA is because of the hybridization of plasmon polariton Bloch wave and the electronic resonance of the heme group of CYP2J2. We found the plasmonic properties of the nanoLCA sensor to be highly reproducible, which allowed comparisons among the different substrates at different concentrations. Further, due to the unique spectral properties of the nanoLCA sensor, including the transmission of a single color, we were able to perform colorimetric detection of the binding events. These results indicate that a resonance plasmonic sensing mechanism can be used to distinguish between different substrates of the same binding type at different concentrations binding to P450s and that the nanoLCA sensor has the potential to provide consistent high-throughput measurements of this system.

Injection-seeded optoplasmonic amplifier in the visible.

A hybrid optoplasmonic amplifier, injection-seeded by an internally-generated Raman signal and operating in the visible (563-675 nm), is proposed and evidence for amplification is presented. Comprising a gain medium tethered to a whispering gallery mode (WGM) resonator with a protein, and a plasmonic surface, the optical system described here selectively amplifies a single (or a few) Raman line(s) produced within the WGM resonator and is well-suited for routing narrowband optical power on-a-chip. Over the past five decades, optical oscillators and amplifiers have typically been based on the buildup of the field from the spontaneous emission background. Doing so limits the temporal coherence of the output, lengthens the time required for the optical field intensity to reach saturation, and often is responsible for complex, multiline spectra. In addition to the spectral control afforded by injection-locking, the effective Q of the amplifier can be specified by the bandwidth of the injected Raman signal. This characteristic contrasts with previous WGM-based lasers and amplifiers for which the Q is determined solely by the WGM resonator.

A wafer-scale backplane-assisted resonating nanoantenna array SERS device created by tunable thermal dewetting nanofabrication.

A tunable lithography-less nanofabrication process using a metal thin-film thermal dewetting technique has been developed to fabricate wafer-scale and uniform plasmonic substrates at low cost for optimal performance in surface enhanced Raman scattering (SERS) applications. The relationship between the tunable parameters of this process and the corresponding optical and plasmonic characteristic is investigated both experimentally and theoretically to understand the deterministic design of an optimal SERS device with a three-dimensional plasmonic nanoantenna structure. The enhancement of SERS using various nanoplasmonic particle sizes, structure lengths, lateral hot spot spacings and resonating effects are examined and demonstrated. We achieve a uniform optimal enhancement factor of 1.38 × 10(8) on a 4 in wafer-scale SERS substrate with a backplane-assisted resonating nanoantenna array design. Sensitive environmental nitrate sensing, vitamin detection and oligonucleotide identification are demonstrated on the high-performance SERS device.

The microelectronic wireless nitrate sensor network for environmental water monitoring.

Quantitative monitoring of water conditions in a field is a critical ability for environmental science studies. We report the design, fabrication and testing of a low cost, miniaturized and sensitive electrochemical based nitrate sensor for quantitative determination of nitrate concentrations in water samples. We have presented detailed analysis for the nitrate detection results using the miniaturized sensor. We have also demonstrated the integration of the sensor to a wireless network and carried out field water testing using the sensor. We envision that the field implementation of the wireless water sensor network will enable "smart farming" and "smart environmental monitoring".