Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy.

Tumour-derived exosomes (T-EXOs) impede immune checkpoint blockade therapies, motivating pharmacological efforts to inhibit them. Inspired by how antiviral curvature-sensing peptides disrupt membrane-enveloped virus particles in the exosome size range, we devised a broadly useful strategy that repurposes an engineered antiviral peptide to disrupt membrane-enveloped T-EXOs for synergistic cancer immunotherapy. The membrane-targeting peptide inhibits T-EXOs from various cancer types and exhibits pH-enhanced membrane disruption relevant to the tumour microenvironment. The combination of T-EXO-disrupting peptide and programmed cell death protein-1 antibody-based immune checkpoint blockade therapy improves treatment outcomes in tumour-bearing mice. Peptide-mediated disruption of T-EXOs not only reduces levels of circulating exosomal programmed death-ligand 1, but also restores CD8+ T cell effector function, prevents premetastatic niche formation and reshapes the tumour microenvironment in vivo. Our findings demonstrate that peptide-induced T-EXO depletion can enhance cancer immunotherapy and support the potential of peptide engineering for exosome-targeting applications.

Time-asymmetric loop around an exceptional point over the full optical communications band.

Topological operations around exceptional points1-8-time-varying system configurations associated with non-Hermitian singularities-have been proposed as a robust approach to achieving far-reaching open-system dynamics, as demonstrated in highly dissipative microwave transmission3 and cryogenic optomechanical oscillator4 experiments. In stark contrast to conventional systems based on closed-system Hermitian dynamics, environmental interferences at exceptional points are dynamically engaged with their internal coupling properties to create rotational stimuli in fictitious-parameter domains, resulting in chiral systems that exhibit various anomalous physical phenomena9-16. To achieve new wave properties and concomitant device architectures to control them, realizations of such systems in application-abundant technological areas, including communications and signal processing systems, are the next step. However, it is currently unclear whether non-Hermitian interaction schemes can be configured in robust technological platforms for further device engineering. Here we experimentally demonstrate a robust silicon photonic structure with photonic modes that transmit through time-asymmetric loops around an exceptional point in the optical domain. The proposed structure consists of two coupled silicon-channel waveguides and a slab-waveguide leakage-radiation sink that precisely control the required non-Hermitian Hamiltonian experienced by the photonic modes. The fabricated devices generate time-asymmetric light transmission over an extremely broad spectral band covering the entire optical telecommunications window (wavelengths between 1.26 and 1.675 micrometres). Thus, we take a step towards broadband on-chip optical devices based on non-Hermitian topological dynamics by using a semiconductor platform with controllable optoelectronic properties, and towards several potential practical applications, such as on-chip optical isolators and non-reciprocal mode converters. Our results further suggest the technological relevance of non-Hermitian wave dynamics in various other branches of physics, such as acoustics, condensed-matter physics and quantum mechanics.

Synthetic Topological Nodal Phase in Bilayer Resonant Gratings.

The notion of synthetic dimensions in artificial photonic systems has received considerable attention as it provides novel methods for exploring hypothetical topological phenomena as well as potential device applications. Here, we present nanophotonic manifestation of a two-dimensional topological nodal phase in bilayer resonant grating structures. Using the mathematical analogy between a topological semimetal and vertically asymmetric photonic lattices, we show that the interlayer shift simulates an extra momentum dimension for creating a two-dimensional topological nodal phase. We present a theoretical model and rigorous numerical analyses showing the two nodal points that produce a complex gapless band structure and localized edge states in the topologically nontrivial region. Therefore, our results provide a practical scheme for producing high-dimensional topological effects in simple low-dimensional photonic structures.

Development of a novel multifocal lens using a polarization directed flat lens: possible candidate for a multifocal intraocular lens.

BACKGROUND: A polarization-directed flat (PDF) lens acts as a converging lens with a focal length (f) > 0 and a diverging lens with f < 0, depending on the polarization state of the incidental light. To produce a multifocal lens with two focal lengths, a PDF and a converging lens having shorter focal length were combined. In this study, we tested a bifocal PDF to determine its potential as a new multifocal intraocular lens (IOL). METHODS: Constructed a multifocal lens with a PDF lens (f = +/- 100 mm) and a converging lens (f = + 25 mm). In an optical bench test, we measured the defocus curve to test the multifocal function. The multifocal function and optical quality of the lens in various situations were tested. An Early Treatment Diabetic Retinopathy Study (ETDRS) chart as a near target and a building as a distant target were photographed using a digital single-lens reflex (DSLR) camera. Both lenses (multifocal and monofocal) were tested under the same conditions. RESULTS: For the 0 D and - 20 D focal points, the multifocal lens showed sharp images in the optical bench test. In the DSLR test using the multifocal lens, the building appeared slightly blurry compared with the results using the monofocal lens. With the multifocal lens, the ETDRS chart's images became blurry as the ETDRS chart's distance decreased, but became very clear again at a certain position. CONCLUSIONS: We confirmed the multifocal function of the multifocal lens using a PDF lens. This lens can be used as a multifocal IOL in the future.

Nanofabrication of plasmonic structures on insulating substrates by resist-on-metal bilayer lift-off.

In last few decades, micro- and nano-fabrication techniques based on photolithography and electron beam lithography have advanced greatly, mainly in the field of semiconductor fabrication. Such techniques are generally transferrable to the fabrication of plasmonic structures and metamaterials. However, plasmonic devices often require a transparent insulating substrate to be operational at visible or near-infrared wavelengths. Here we report a resist-on-metal bilayer lift-off technique enabling the fabrication of plasmonic structures on insulating substrates. The metal layer under the resist eliminates major difficulties in lithography, such as charging during electron beam exposure and uncontrolled diffuse optical scattering during photolithography. In addition, the resist-on-metal bilayer can be migrated to different substrates with minimal process alteration, because the material properties of the substrate, such as secondary electron emission or optical reflectance, become irrelevant due to the shielding provided by the metal layer. As demonstrations, we fabricate large-scale plasmonic waveguides and Bragg gratings, adiabatically-modulated plasmonic waveguide couplers, and plasmonic nanoantenna arrays using the resist-on-metal bilayer lift-off process. The process can also be used to define structures formed of other materials such as dielectrics.

CMOS-compatible Si metasurface at visible wavelengths prepared by low-temperature green laser annealing.

A low-temperature laser crystallization is newly devised for producing polycrystalline silicon (poly-Si) thin films of low-loss, low surface roughness enough for nanoscale patterning, applicable to practical Si metasurface elements on complementary metal-oxide semiconductor (CMOS) electronic architectures in visible lights. The method is based on dielectric encapsulation of an amorphous Si film and subsequent laser-induced local crystallization. Such poly-Si thin film yields order-of-magnitude smaller surface roughness and grain size than those obtained with the conventional laser annealing processes. The mechanism of the formation of small and uniform crystalline grains during solidification is studied to ensure the smooth surfaces enough for nanoscale patterning. By obtaining root mean square of surface roughness <2.49 nm and extinction coefficient <4.8 × 10-2 at 550 nm, visible metasurface color-filter elements are experimentally demonstrated with the resonant transmission-peak efficiency approaching ∼85%. This low-loss poly-Si metasurface is favorably compatible with embedded CMOS electronic architectures in contrast to the conventional thermal annealing processes that often cause failure of electrical device functionalities due to delamination and material-property degradation problems. The proposed fabrication in this study provides a practical method for further development of various Si metasurfaces in the visible domain and their integration with CMOS electronic devices as well.

Quantum plasmonic sensing using single photons.

Reducing the noise below the shot-noise limit in sensing devices is one of the key promises of quantum technologies. Here, we study quantum plasmonic sensing based on an attenuated total reflection configuration with single photons as input. Our sensor is the Kretschmann configuration with a gold film, and a blood protein in an aqueous solution with different concentrations serves as an analyte. The estimation of the refractive index is performed using heralded single photons. We also determine the estimation error from a statistical analysis over a number of repetitions of identical and independent experiments. We show that the errors of our plasmonic sensor with single photons are below the shot-noise limit even in the presence of various experimental imperfections. Our results demonstrate a practical application of quantum plasmonic sensing is possible given certain improvements are made to the setup investigated, and pave the way for a future generation of quantum plasmonic applications based on similar techniques.

Mixture risk assessment of selected mainstream cigarette smoke constituents generated from low-yield cigarettes in South Korean smokers.

A total of 38 hazardous constituents in mainstream cigarette smoke of low-yield cigarettes sold in Korea were selected and analyzed using established methods. Risk calculations were performed using risk algorithms employed in previous studies and Korean population-based exposure parameters. The median cumulative incremental lifetime cancer risk of male smokers could vary from 828 × 10-6 to 2510 × 10-6, and that of female smokers could range from 440 × 10-6 to 1300 × 10-6, depending on the smoking regimens. The median hazard index as the sum of hazard quotients of male smokers varied from 367 to 1,225, and that of female smokers varied from 289 to 970, depending on the smoking regimens. The sensitivity analysis for this risk assessment indicated that the constituent yields in mainstream cigarette smoke, average number of cigarettes smoked per day or year, and mouth-spill rate are the main risk factors. Statistical positive correlations between the average daily dose calculated by the exposure algorithm used in this study for individual smokers and biomarkers verified the reliability of this assessment. It could be concluded that inhalation of the constituents present in the mainstream of low-yield cigarettes has significant cancer and non-cancer health risks, although its effect on risk reduction is still unknown under the fixed machine-smoking conditions.

Electrically tunable binary phase Fresnel lens based on a dielectric elastomer actuator.

We propose and demonstrate an all-solid-state tunable binary phase Fresnel lens with electrically controllable focal length. The lens is composed of a binary phase Fresnel zone plate, a circular acrylic frame, and a dielectric elastomer (DE) actuator which is made of a thin DE layer and two compliant electrodes using silver nanowires. Under electric potential, the actuator produces in-plane deformation in a radial direction that can compress the Fresnel zones. The electrically-induced deformation compresses the Fresnel zones to be contracted as high as 9.1% and changes the focal length, getting shorter from 20.0 cm to 14.5 cm. The measured change in the focal length of the fabricated lens is consistent with the result estimated from numerical simulation.

Single-mode lasers and parity-time symmetry broken gratings based on active dielectric-loaded long-range surface plasmon polariton waveguides.

Single-mode distributed feedback laser structures and parity-time symmetry broken grating structures based on dielectric-loaded long-range surface plasmon polariton waveguides are proposed. The structures comprise a thin Ag stripe on an active polymer bottom cladding with an active polymer ridge. The active polymer assumed is PMMA doped with IR140 dye providing optical gain at near infrared wavelengths. Cutoff top ridge dimensions (thickness and width) are calculated using a finite element method and selected to guarantee single-mode operation of the laser. Several parameters such as the threshold number of periods and the lasing wavelength are determined using the transfer matrix method. A related structure based on two pairs of waveguides of two widths, which have the same imaginary part but different real part of effective index, arranged within one grating period, is proposed as an active grating operating at the threshold for parity-time symmetry breaking (i.e., operating at an exceptional point). Such "exceptional point" gratings produce ideal reflectance asymmetry as demonstrated via transfer matrix computations.

Temperature and gain tuning of plasmonic coherent perfect absorbers.

We experimentally demonstrate temperature-tuned and gain-assisted surface-plasmonic coherent perfect absorbers. In these devices, coherent perfect absorption (CPA) is supported by balancing the absorber's radiative and non-radiative decay rates under thermal tuning of free-electron collision frequency in the Ag layer and optical tuning of the amplification rate in the adjacent dielectric film with optical gain, respectively. The results show that these methods are experimentally feasible and applicable to various CPA configurations.

Parity-time-symmetry breaking in double-slab surface-plasmon-polariton waveguides.

We theoretically demonstrate spontaneous PT-symmetry breaking behavior of surface-plasmon polaritons (SPP) in coupled double-slab (DS) waveguides. By virtue of a flat-top field at critical wavelength, the imaginary index of a DS-SPP mode can be controlled via changing the core thickness, while the real index is kept constant. Therefore, a waveguide coupler that consists of a pair of DS-SPP waveguides with different core thicknesses can represent a passive PT-symmetric system, which always maintains symmetry under a real potential. This set-up also represents a good opportunity to investigate the underlying physics of PT-symmetry breaking in non-Hermitian Hamiltonian systems.

Gain-assisted critical coupling for high-performance coherent perfect absorbers.

Balanced radiation and absorption rates of an optical resonator are necessary for coherent perfect light absorption in many active device applications. This balance is referred to as critical coupling condition. We propose a gain-assisted method for exact access to critical coupling conditions without altering any structure parameters. In a coherent absorber with additional internal gain media, critical coupling with arbitrarily high coherent signal extinction can be obtained by continuously tuning optical pumping density. Assuming a surface-plasmon resonance grating covered by a gain layer as a promising architecture, we numerically demonstrate gain-assisted continuous access to its critical coupling point with experimentally probable settings. In addition, the gain tuning further introduces switching of the coherent-absorber's functionality to a conventional lossless beam splitter.

FDTD simulation of transmittance characteristics of one-dimensional conducting electrodes.

We investigated transparent conducting electrodes consisting of periodic one-dimensional Ag or Al grids with widths from 25 nm to 5 µm via the finite-difference time-domain method. To retain high transmittance, two grid configurations with opening ratios of 90% and 95% were simulated. Polarization-dependent characteristics of the transmission spectra revealed that the overall transmittance of micron-scale grid electrodes may be estimated by the sum of light power passing through the uncovered area and the light power penetrating the covered metal layer. However, several dominant physical phenomena significantly affect the transmission spectra of the nanoscale grids: Rayleigh anomaly, transmission decay in TE polarized mode, and localized surface plasmon resonance. We conclude that, for applications of transparent electrodes, the critical feature sizes of conducting 1D grids should not be less than the wavelength scale in order to maintain uniform and predictable transmission spectra and low electrical resistivity.

Experimental observation of electroluminescence enhancement on green LEDs mediated by surface plasmons.

We experimentally demonstrate the 1.5-fold enhancement of the electroluminescence (EL) of surface-plasmon (SP)-mediated green LEDs. On the p-clad surface of InGaN/GaN multi-quantum well LEDs, a 2-dimensional, second-order grating structure is textured and coated with an Ag electrode. With this setup, a larger EL enhancement factor is obtained at a higher injected current, which suggests that SP-LEDs can be a possible solution to efficiency droop, which is one of the main problems in developing high-power LEDs. Details regarding the implementation of our device are discussed.

Synthesis of Cu or Cu2O-polyimide nanocomposites using Cu powders and their optical properties.

Nanocomposites consisting of Cu or Cu2O nanoparticles in various polyimide (PI) films were successfully prepared using polyamic acid (PAA) and Cu powders. Cu powders were dissolved into PAA solutions, and the solutions were spin-coated onto the substrates. Cu or Cu2O nanoparticles were formed in PI film by curing in a reducing or inert atmosphere, respectively. The Cu nanoparticles were transformed to Cu2O nanoparticles by post-heat treatment in an oxidizing atmosphere after curing in a reducing atmosphere. Transmission electron microscopy showed that uniform, round Cu2O nanoparticles 6.0 nm in diameter were dispersed in the PI film by post-heat treatment. The addition of Cu2O nanoparticles in the 4,4'-(hexafluoroisopropylidene)diphthalic anhydride-4,4'-oxydianiline (6FDA-ODA) PI film enhanced the refractive index of the 6FDA-ODA PI film from 1.60 to 1.72 at 633 nm, and the transparency of the nanocomposite film was about 70-90% in the visible region and remained around 90% beyond 550 nm.

Self-immolative polymer-based immunogenic cell death inducer for regulation of redox homeostasis.

Doxorubicin (DOX), widely used as an anticancer drug, is considered an immunogenic cell death (ICD) inducer that enhances cancer immunotherapy. However, its extended application as an ICD inducer has been limited owing to poor antigenicity and inefficient adjuvanticity. To enhance the immunogenicity of DOX, we prepare a reactive oxygen species (ROS)-responsive self-immolative polymer (R-SIP) that can efficiently destroy redox homeostasis via self-immolation-mediated glutathione depletion in cancer cells. Owing to its amphiphilic nature, R-SIP self-assemble into nano-sized particles under aqueous conditions, and DOX is efficiently encapsulated inside the nanoparticles by a simple dialysis method. Interestingly, when treated with 4T1 cancer cells, DOX-encapsulated R-SIP (DR-SIP) induces the phosphorylation of eukaryotic translation initiation factor 2α and overexpression of ecto-calreticulin, resulting in endoplasmic reticulum-associated ICD. In addition, DR-SIP contributes to the maturation of dendritic cells by promoting the release of damage-associated molecular patterns (DAMPs) from cancer cells. When intravenously administered to tumor-bearing mice, DR-SIP remarkably inhibits tumor growth compared with DOX alone. Overall, DR-SIP may have the potential to elicit an immune response as an ICD inducer.

Functionally Masked Antibody to Uncouple Immune-Related Toxicities in Checkpoint Blockade Cancer Therapy.

Of the existing immunotherapy drugs in oncology, monoclonal antibodies targeting the immune checkpoint axis are preferred because of the durable responses observed in selected patients. However, the associated immune-related adverse events (irAEs), causing uncommon fatal events, often require specialized management and medication discontinuation. The study aim was to investigate our hypothesis that masking checkpoint antibodies with tumor microenvironment (TME)-responsive polymer chains can mitigate irAEs and selectively target tumors by limiting systemic exposure to patients. We devised a broadly applicable strategy that functionalizes immune checkpoint-blocking antibodies with a mildly acidic pH-cleavable poly(ethylene glycol) (PEG) shell to prevent inflammatory side effects in normal tissues. Conjugation of pH-sensitive PEG to anti-CD47 antibodies (αCD47) minimized antibody-cell interactions by inhibiting their binding ability and functionality at physiological pH, leading to prevention of αCD47-induced anemia in tumor-bearing mice. When conjugated to anti-CTLA-4 and anti-PD-1 antibodies, double checkpoint blockade-induced colitis was also ameliorated. Notably, removal of the protective shell in response to an acidic TME restored the checkpoint antibody activities, accompanied by effective tumor regression and long-term survival in the mouse model. Our results support a feasible strategy for antibody-based therapies to uncouple toxicity from efficacy and show the translational potential for cancer immunotherapy.

Polarization-extinction-based detection of DNA hybridization in situ using a nanoparticle wire-grid polarizer.

Metallic wires can discriminate light polarization due to strong absorption of electric fields oscillating in parallel to wires. Here, we explore polarization-based biosensing of DNA hybridization in situ by employing metal target-conjugated nanoparticles to form a wire-grid polarizer (WGP) as complementary DNA strands hybridize. Experimental results using gold nanoparticles of 15 nm diameter to form a WGP of 400 nm period suggest that polarization extinction can detect DNA hybridization with a limit of detection in the range of 1 nM concentration. The sensitivity may be improved by more than an order of magnitude if larger nanoparticles are employed to define WGPs at a period between 400 and 500 nm.

Measurement and modeling of a complete optical absorption and scattering by coherent surface plasmon-polariton excitation using a silver thin-film grating.

We demonstrate the plasmonic analogue of a coherent photonic effect known as coherent perfect absorption. A periodically nanopatterned metal film perfectly absorbs multiple coherent light beams coupling to a single surface plasmon mode. The perfect absorbing state can be switched to a nearly perfect scattering state by tuning the phase difference between the incident beams. We theoretically explain the plasmonic coherent perfect absorption by considering time-reversal symmetry of surface plasmon amplification by stimulated emission of radiation. We experimentally demonstrate coherent control of the plasmonic absorption in good agreement with a coupled-mode theory of dissipative resonances. Associated potential applications include absorption-based plasmonic switches, modulators, and light-electricity transducers.