Polphylipoprotein-induced autophagy mechanism with high performance in photodynamic therapy.

Polphylipoprotein (PLP) is a recently developed nanoparticle with high biocompatibility and tumor selectivity, and which has demonstrated unprecedentedly high performance photosensitizer in photodynamic therapy (PDT) and photodynamic diagnosis. On the basis of these discoveries, PLP is anticipated to have a very high potential for PDT. However, the mechanism by which PLP kills cancer cells effectively has not been sufficiently clarified. To comprehensively understand the PLP-induced PDT processes, we conduct multifaceted experiments using both normal cells and cancer cells originating from the same sources, namely, RGM1, a rat gastric epithelial cell line, and RGK1, a rat gastric mucosa-derived cancer-like mutant. We reveal that PLP enables highly effective cancer treatment through PDT by employing a unique mechanism that utilizes the process of autophagy. The dynamics of PLP-accumulated phagosomes immediately after light irradiation are found to be completely different between normal cells and cancer cells, and it becomes clear that this difference results in the manifestation of the characteristic effect of PDT when using PLP. Since PLP is originally developed as a drug delivery agent, this study also suggests the potential for intracellular drug delivery processes through PLP-induced autophagy.

Cell-Level Analysis Visualizing Photodynamic Therapy with Porphylipoprotein and Talaporphyrin Sodium.

We revealed the difference in the mechanism of photodynamic therapy (PDT) between two photosensitizers: porphylipoprotein (PLP), which has recently attracted attention for its potential to be highly effective in treating cancer, and talaporphyrin sodium (NPe6). (1) NPe6 accumulates in lysosomes, whereas PLP is incorporated into phagosomes formed by PLP injection. (2) PDT causes NPe6 to generate reactive oxygen species, thereby producing actin filaments and stress fibers. In the case of PLP, however, reactive oxygen species generated by PDT remain in the phagosomes until the phagosomal membrane is destroyed, which delays the initiation of RhoA activation and RhoA*/ROCK generation. (4) After the disruption of the phagosomal membrane, however, the outflow of various reactive oxygen species accelerates the production of actin filaments and stress fibers, and blebbing occurs earlier than in the case of NPe6. (5) PLP increases the elastic modulus of cells without RhoA activity in the early stage. This is because phagosomes are involved in polymerizing actin filaments and pseudopodia formation. Considering the high selectivity and uptake of PLP into cancer cells, a larger effect with PDT can be expected by skillfully combining the newly discovered characteristics, such as the appearance of a strong effect at an early stage.

High-throughput terahertz spectral line imaging using an echelon mirror.

This work demonstrates terahertz (THz) line imaging that acquires broadband spectral information by combining echelon-based single-shot THz spectroscopy with high-sensitivity phase-offset electrooptic detection. An approximately 40 dB signal-to-noise ratio is obtained for a THz spectrum from a single line of the camera, with a detection bandwidth up to 2 THz at the peak electric-field strength of 1.2 kV/cm. The spatial resolution of the image is confirmed to be diffraction limited for each spectral component of the THz wave. We use the system to image sugar tablets by quickly scanning the sample, which illustrates the capacity of the proposed spectral line imaging system for high-throughput applications.

Subcycle mid-infrared coherent transients at 4 MHz repetition rate applicable to light-wave-driven scanning tunneling microscopy.

We produce subcycle mid-infrared (MIR) pulses at a 4 MHz repetition rate via the optical rectification (OR) of sub-10 fs near-infrared pulses delivered by an optical parametric chirped pulse amplifier. The coherent MIR pulses generated in a GaSe crystal under an ultrabroadband phase-matching condition contain only 0.58-0.85 oscillation cycles within the full width at half-maximum of the intensity envelope. The use of OR enables excellent phase stability of 56 mrad over 5.6 h, which is confirmed by field-resolved detection using electro-optic sampling. An electromagnetic simulation using a finite integration technique reveals that the peak field strength can easily exceed 10 V/nm owing to the field enhancement resulting from focusing MIR pulses onto a tunnel junction.

Selective Reduction Mechanism of Graphene Oxide Driven by the Photon Mode versus the Thermal Mode.

A two-dimensional nanocarbon, graphene, has attracted substantial interest due to its excellent properties. The reduction of graphene oxide (GO) has been investigated for the mass production of graphene used in practical applications. Different reduction processes produce different properties in graphene, affecting the performance of the final materials or devices. Therefore, an understanding of the mechanisms of GO reduction is important for controlling the properties of functional two-dimensional systems. Here, we determined the average structure of reduced GO prepared via heating and photoexcitation and clearly distinguished their reduction mechanisms using ultrafast time-resolved electron diffraction, time-resolved infrared vibrational spectroscopy, and time-dependent density functional theory calculations. The oxygen atoms of epoxy groups are selectively removed from the basal plane of GO by photoexcitation (photon mode), in stark contrast to the behavior observed for the thermal reduction of hydroxyl and epoxy groups (thermal mode). The difference originates from the selective excitation of epoxy bonds via an electronic transition due to their antibonding character. This work will enable the preparation of the optimum GO for the intended applications and expands the application scope of two-dimensional systems.

Surface-mediated spin dynamics probed by optical-pump-probe scanning tunneling microscopy.

In current materials science and technologies, surface effects on carrier and spin dynamics in functional materials and devices are of great importance. In this paper, we present the surface-sensitive probing of electron spin dynamics, performed by optical-pump-probe scanning tunneling microscopy (OPP-STM). Time-resolved spin lifetime information on a manganese (Mn)-deposited GaAs(110) surface was successfully obtained for the first time. With increasing Mn density via in situ evaporation, a nonlinear change in the spin lifetime in the picosecond range was clearly observed, while directly confirming the Mn density by STM. In comparison with the results obtained by the conventional OPP method, we have also demonstrated that the observed nonlinear spin lifetime behavior was surface-mediated, which can be characterized using only the surface-sensitive OPP-STM technique.

Fast-frame single-shot pump-probe spectroscopy with chirped-fiber Bragg gratings.

To acquire single-shot pump-probe waveforms for each laser pulse at a high repetition rate and high signal-to-noise ratio, we combined the photonic time-stretch technique and time-encoding method using a chirped-fiber Bragg grating (CFBG) and a grating-pair pulse compressor. By changing the pre-chirping of the probe pulse, a variable time window of the pump-probe traces from 1.4 to 17 ps was demonstrated. The use of a CFBG improved the signal-to-noise ratio of the waveforms by minimizing the loss of probe pulses due to the transmission through a long fiber. These techniques are promising, for example, in applications in multi-timescale pump-probe spectroscopy of irreversible phenomena.

Simultaneous acquisition of complex transmittance and birefringence with two counter-rotating, circularly polarized THz pulses.

Here we demonstrate simultaneous measurements of the complex transmittance and birefringence using left- and right-handed circularly polarized terahertz (THz) pulses. We change the polarization of the THz pulses periodically by modulating the polarization of the pump pulses directed onto a ZnTe (111) crystal, and we convert linear to circular polarization using a broadband THz quarter-wave retarder. By integrating the alternating-emission system with the polarization-sensitive terahertz time-domain spectrometer, we are able to obtain the electric-field vector of the transmitted terahertz pulses for both the left- and right-handed circular polarizations. Utilizing this technique, we are able to measure simultaneously the frequency-dependent complex refractive indices (real and imaginary parts) and the orientations of the slow and fast axes of birefringent materials, a quartz disc and a barium borate crystal, in a single temporal sweep.

Tailoring Single-Cycle Near Field in a Tunnel Junction with Carrier-Envelope Phase-Controlled Terahertz Electric Fields.

Light-field-driven processes occurring under conditions far beyond the diffraction limit of the light can be manipulated by harnessing spatiotemporally tunable near fields. A tailor-made carrier envelope phase in a tunnel junction formed between nanogap electrodes allows precisely controlled manipulation of these processes. In particular, the characterization and active control of near fields in a tunnel junction are essential for advancing elaborate manipulation of light-field-driven processes at the atomic-scale. Here, we demonstrate that desirable phase-controlled near fields can be produced in a tunnel junction via terahertz scanning tunneling microscopy (THz-STM) with a phase shifter. Measurements of the phase-resolved subcycle electron tunneling dynamics revealed an unexpected large carrier-envelope phase shift between far-field and near-field single-cycle THz waveforms. The phase shift stems from the wavelength-scale feature of the tip-sample configuration. By using a dual-phase double-pulse scheme, the electron tunneling was coherently manipulated over the femtosecond time scale. Our new prescription-in situ tailoring of single-cycle THz near fields in a tunnel junction-will offer unprecedented control of electrons for ultrafast atomic-scale electronics and metrology.