Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae.

Mammals cannot see light over 700 nm in wavelength. This limitation is due to the physical thermodynamic properties of the photon-detecting opsins. However, the detection of naturally invisible near-infrared (NIR) light is a desirable ability. To break this limitation, we developed ocular injectable photoreceptor-binding upconversion nanoparticles (pbUCNPs). These nanoparticles anchored on retinal photoreceptors as miniature NIR light transducers to create NIR light image vision with negligible side effects. Based on single-photoreceptor recordings, electroretinograms, cortical recordings, and visual behavioral tests, we demonstrated that mice with these nanoantennae could not only perceive NIR light, but also see NIR light patterns. Excitingly, the injected mice were also able to differentiate sophisticated NIR shape patterns. Moreover, the NIR light pattern vision was ambient-daylight compatible and existed in parallel with native daylight vision. This new method will provide unmatched opportunities for a wide variety of emerging bio-integrated nanodevice designs and applications. VIDEO ABSTRACT.

A self-healing multispectral transparent adhesive peptide glass.

Despite its disordered liquid-like structure, glass exhibits solid-like mechanical properties1. The formation of glassy material occurs by vitrification, preventing crystallization and promoting an amorphous structure2. Glass is fundamental in diverse fields of materials science, owing to its unique optical, chemical and mechanical properties as well as durability, versatility and environmental sustainability3. However, engineering a glassy material without compromising its properties is challenging4-6. Here we report the discovery of a supramolecular amorphous glass formed by the spontaneous self-organization of the short aromatic tripeptide YYY initiated by non-covalent cross-linking with structural water7,8. This system uniquely combines often contradictory sets of properties; it is highly rigid yet can undergo complete self-healing at room temperature. Moreover, the supramolecular glass is an extremely strong adhesive yet it is transparent in a wide spectral range from visible to mid-infrared. This exceptional set of characteristics is observed in a simple bioorganic peptide glass composed of natural amino acids, presenting a multi-functional material that could be highly advantageous for various applications in science and engineering.

Thermal infrared directs host-seeking behaviour in Aedes aegypti mosquitoes.

Mosquito-borne diseases affect hundreds of millions of people annually and disproportionately impact the developing world1,2. One mosquito species, Aedes aegypti, is a primary vector of viruses that cause dengue, yellow fever and Zika. The attraction of Ae. aegypti female mosquitos to humans requires integrating multiple cues, including CO2 from breath, organic odours from skin and visual cues, all sensed at mid and long ranges, and other cues sensed at very close range3-6. Here we identify a cue that Ae. aegypti use as part of their sensory arsenal to find humans. We demonstrate that Ae. aegypti sense the infrared (IR) radiation emanating from their targets and use this information in combination with other cues for highly effective mid-range navigation. Detection of thermal IR requires the heat-activated channel TRPA1, which is expressed in neurons at the tip of the antenna. Two opsins are co-expressed with TRPA1 in these neurons and promote the detection of lower IR intensities. We propose that radiant energy causes local heating at the end of the antenna, thereby activating temperature-sensitive receptors in thermosensory neurons. The realization that thermal IR radiation is an outstanding mid-range directional cue expands our understanding as to how mosquitoes are exquisitely effective in locating hosts.

Thermophotovoltaic efficiency of 40.

Thermophotovoltaics (TPVs) convert predominantly infrared wavelength light to electricity via the photovoltaic effect, and can enable approaches to energy storage1,2 and conversion3-9 that use higher temperature heat sources than the turbines that are ubiquitous in electricity production today. Since the first demonstration of 29% efficient TPVs (Fig. 1a) using an integrated back surface reflector and a tungsten emitter at 2,000 °C (ref. 10), TPV fabrication and performance have improved11,12. However, despite predictions that TPV efficiencies can exceed 50% (refs. 11,13,14), the demonstrated efficiencies are still only as high as 32%, albeit at much lower temperatures below 1,300 °C (refs. 13-15). Here we report the fabrication and measurement of TPV cells with efficiencies of more than 40% and experimentally demonstrate the efficiency of high-bandgap tandem TPV cells. The TPV cells are two-junction devices comprising III-V materials with bandgaps between 1.0 and 1.4 eV that are optimized for emitter temperatures of 1,900-2,400 °C. The cells exploit the concept of band-edge spectral filtering to obtain high efficiency, using highly reflective back surface reflectors to reject unusable sub-bandgap radiation back to the emitter. A 1.4/1.2 eV device reached a maximum efficiency of (41.1 ± 1)% operating at a power density of 2.39 W cm-2 and an emitter temperature of 2,400 °C. A 1.2/1.0 eV device reached a maximum efficiency of (39.3 ± 1)% operating at a power density of 1.8 W cm-2 and an emitter temperature of 2,127 °C. These cells can be integrated into a TPV system for thermal energy grid storage to enable dispatchable renewable energy. This creates a pathway for thermal energy grid storage to reach sufficiently high efficiency and sufficiently low cost to enable decarbonization of the electricity grid.

The deSUMOylase SENP2 coordinates homologous recombination and nonhomologous end joining by independent mechanisms.

SUMOylation (small ubiquitin-like modifier) in the DNA double-strand break (DSB) response regulates recruitment, activity, and clearance of repair factors. However, our understanding of a role for deSUMOylation in this process is limited. Here we identify different mechanistic roles for deSUMOylation in homologous recombination (HR) and nonhomologous end joining (NHEJ) through the investigation of the deSUMOylase SENP2. We found that regulated deSUMOylation of MDC1 prevents excessive SUMOylation and its RNF4-VCP mediated clearance from DSBs, thereby promoting NHEJ. In contrast, we show that HR is differentially sensitive to SUMO availability and SENP2 activity is needed to provide SUMO. SENP2 is amplified as part of the chromosome 3q amplification in many cancers. Increased SENP2 expression prolongs MDC1 focus retention and increases NHEJ and radioresistance. Collectively, our data reveal that deSUMOylation differentially primes cells for responding to DSBs and demonstrates the ability of SENP2 to tune DSB repair responses.

Symmetry-breaking malachite green as a near-infrared light-activated fluorogenic photosensitizer for RNA proximity labeling.

Cellular RNA is asymmetrically distributed in cells and the regulation of RNA localization is crucial for proper cellular functions. However, limited chemical tools are available to capture dynamic RNA localization in complex biological systems with high spatiotemporal resolution. Here, we developed a new method for RNA proximity labeling activated by near-infrared (NIR) light, which holds the potential for deep penetration. Our method, termed FAP-seq, utilizes a genetically encoded fluorogen activating protein (FAP) that selectively binds to a set of substrates known as malachite green (MG). FAP binding restricts the rotation of MG and rapidly activates its fluorescence in a wash-free manner. By introducing a monoiodo modification to MG, we created a photosensitizer (MG-HI) with the highest singlet oxygen generation ability among various MG derivatives, enabling both protein and RNA proximity labeling in live cells. New insights are provided in the transcriptome analysis with FAP-seq, while a deeper understanding of the symmetry-breaking structural arrangement of FAP-MG-HI was obtained through molecular dynamics simulations. Overall, our wash-free and NIR light-inducible RNA proximity labeling method (FAP-seq) offers a powerful and versatile approach for investigating complex mechanisms underlying RNA-related biological processes.

Photoredox catalysis using infrared light via triplet fusion upconversion.

Recent advances in photoredox catalysis have made it possible to achieve various challenging synthetic transformations, polymerizations and surface modifications1-3. All of these reactions require ultraviolet- or visible-light stimuli; however, the use of visible-light irradiation has intrinsic challenges. For example, the penetration of visible light through most reaction media is very low, leading to problems in large-scale reactions. Moreover, reactants can compete with photocatalysts for the absorption of incident light, limiting the scope of the reactions. These problems can be overcome by the use of near-infrared light, which has a much higher penetration depth through various media, notably biological tissue4. Here we demonstrate various photoredox transformations under infrared radiation by utilizing the photophysical process of triplet fusion upconversion, a mechanism by which two low-energy photons are converted into a higher-energy photon. We show that this is a general strategy applicable to a wide range of photoredox reactions. We tune the upconversion components to adjust the output light, accessing both orange light and blue light from low-energy infrared light, by pairwise manipulation of the sensitizer and annihilator. We further demonstrate that the annihilator itself can be used as a photocatalyst, thus simplifying the reaction. This approach enables catalysis of high-energy transformations through several opaque barriers using low-energy infrared light.

Scalable Drug-Mimicking Nanoplasmonic Therapy for Bradyarrhythmia in Cardiomyocytes.

Bradyarrhythmia poses a serious threat to human health, with chronic progression causing heart failure and acute onset leading to sudden death. In this study, we develop a scalable drug-mimicking nanoplasmonic therapeutic strategy by introducing gold nanorod (Au NR) mediated near-infrared (NIR) photothermal effects. An integrated sensing and regulation platform is established for in situ synchronized NIR laser regulation and electrophysiological property recording. The Au NR plasmonic regulation enables the restoration of normal cardiomyocyte rhythm from the bradyarrhythmia. By regulating the aspect ratio and concentration of Au NRs, as well as the intensity and time of NIR irradiation, we precisely optimized the plasmonic photothermal effect to explore effective therapeutic strategies. Furthermore, mRNA sequencing revealed a significant increase in the number of differentially expressed genes (DEGs) involved in the electrophysiological activities of cardiomyocytes following photothermal therapy. Au NR-mediated plasmonic photothermal therapy, as an efficient and noninvasive approach to bradyarrhythmia, holds profound implications for cardiology research.

Electron-Withdrawing Substituents Enhance the Type I PDT and NIR-II Fluorescence of BODIPY J Aggregates for Bioimaging and Cancer Therapy.

Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.

Phase and Defect Engineering of MoSe2 Nanosheets for Enhanced NIR-II Photothermal Immunotherapy.

Inducing immunogenic cell death (ICD) during photothermal therapy (PTT) has the potential to effectively trigger photothermal immunotherapy (PTI). However, ICD induced by PTT alone is often limited by inefficient PTT, low immunogenicity of tumor cells, and a dysregulated redox microenvironment. Herein, we develop MoSe2 nanosheets with high-percentage metallic 1T phase and rich exposed active Mo centers through phase and defect engineering of MoSe2 as an effective nanoagent for PTI. The metallic 1T phase in MoSe2 nanosheets endows them with strong PTT performance, and the abundant exposed active Mo centers endow them with high activity for glutathione (GSH) depletion. The MoSe2-mediated high-performance PTT synergizing with efficient GSH depletion facilitates the release of tumor-associated antigens to induce robust ICD, thus significantly enhancing checkpoint blockade immunotherapy and activating systemic immune response in mouse models of colorectal cancer and triple-negative metastatic breast cancer.

Disentangling the effects of near-infrared light stimulation and exercise on cognitive function in fNIRS studies.

Functional near-infrared spectroscopy (fNIRS) studies often aim to measure changes in the brain's hemodynamic response in relation to a specific intervention. We recently showed how a fNIRS device could induce photobiomodulatory effects on cognition by using its near-infrared (NIR) light. However, so far, fNIRS research has overlooked the stimulatory potential intrinsic to this technique. The work by Kuwamizu et al. (2023) on pupil dynamics during exercise is no exception. Here, we suggest a fix to their experimental design, which could be taken into account in other fNIRS studies, to guarantee an adequate level of control for possible unconsidered photobiomodulatory effects.

Rational Design of NIR-II G-Quadruplex Fluorescent Probes for Accurate In Vivo Tumor Metastasis Imaging.

Accurate in vivo imaging of G-quadruplexes (G4) is critical for understanding the emergence and progression of G4-associated diseases like cancer. However, existing in vivo G4 fluorescent probes primarily operate within the near-infrared region (NIR-I), which limits their application accuracy due to the short emission wavelength. The transition to second near-infrared (NIR-II) fluorescent imaging has been of significant interest, as it offers reduced autofluorescence and deeper tissue penetration, thereby facilitating more accurate in vivo imaging. Nonetheless, the advancement of NIR-II G4 probes has been impeded by the absence of effective probe design strategies. Herein, through a "step-by-step" rational design approach, we have successfully developed NIRG-2, the first small-molecule fluorescent probe with NIR-II emission tailored for in vivo G4 detection. Molecular docking calculations reveal that NIRG-2 forms stable hydrogen bonds and strong π-π interactions with G4 structures, which effectively inhibit twisted intramolecular charge transfer (TICT) and, thereby, selectively illuminate G4 structures. Due to its NIR-II emission (940 nm), large Stokes shift (90 nm), and high selectivity, NIRG-2 offers up to 47-fold fluorescence enhancement and a tissue imaging depth of 5 mm for in vivo G4 detection, significantly outperforming existing G4 probes. Utilizing NIRG-2, we have, for the first time, achieved high-contrast visualization of tumor metastasis through lymph nodes and precise tumor resection. Furthermore, NIRG-2 proves to be highly effective and reliable in evaluating surgical and drug treatment efficacy in cancer lymphatic metastasis models. We are optimistic that this study not only provides a crucial molecular tool for an in-depth understanding of G4-related diseases in vivo but also marks a promising strategy for the development of clinical NIR-II G4-activated probes.

Tandem Targeting and Dual Aggregation of an AIEgen for Enhanced Near-Infrared Fluorescence Imaging of Tumors.

Near-infrared (NIR) aggregation-induced emission luminogens (AIEgens) are excellent probes for tumor imaging, but there still is space to improve their imaging specificity and sensitivity. In this work, a strategy of tandem targeting and dual aggregation of an AIEgen is proposed to achieve these two purposes. An AIEgen, ß-tBu-Ala-Cys(StBu)-Lys(Biotin)-Pra(QMT)-CBT (Ala-Biotin-QMT), is designed to tandem target the biotin receptor and leucine aminopeptidase of a cancer cell and thereafter undergo CBT-Cys click reaction-mediated dual aggregations in the cell. Experimental results show that Ala-Biotin-QMT renders 4.8-fold and 7.9-fold higher NIR fluorescence signals over those in the "biotin + LAP inhibitor"-treated control groups in living HepG2 cells and HepG2 tumor-bearing mice, respectively. We anticipate that Ala-Biotin-QMT, which has the tandem targeting and dual aggregation property to simultaneously achieve enhanced tumor enrichment and fluorescence onset, could be applied for accurate cancer diagnosis in the clinic in the future.

RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy.

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for the treatment of cancer. Existing photosensitizers are predominantly engineered to target diverse biomolecules, including proteins, DNA, lipids, and carbohydrates, and have proven to greatly enhance the efficacy or specificity of PDT. However, it is noteworthy that there exists a conspicuous scarcity of photosensitizers specifically designed to target RNAs. Recognizing the crucial and multifaceted roles played by RNAs in various cellular processes and disease states, we have ventured into the development of a novel RNA-targeting photosensitizer, named Se-718, designed specifically for PDT-based cancer therapy. Se-718 has been engineered to exhibit a high molar absorption coefficient in the NIR region, which is crucial for effective PDT. More importantly, Se-718 has demonstrated a distinct RNA-targeting capability, as evidenced through rigorous testing in both circular dichroism and fluorescence experiments. Furthermore, Se-718 has been shown to display both type I and type II photodynamic properties. This unique characteristic enables the efficient killing of cancer cells under a wide range of oxygen conditions, both normoxic (21% O2) and hypoxic (2% O2). The IC50 of Se-718 can be as low as 100 nM, and its light-to-dark toxicity ratio is an impressive 215 times higher, outperforming most photosensitizers currently available. Moreover, in vivo studies conducted with tumor-bearing mice have demonstrated the excellent antitumor effects and high safety profile of Se-718. Considering the outstanding PDT efficacy of Se-718, we are optimistic that the development of RNA-targeting photosensitizers may provide an innovative and highly effective option for cancer therapeutics in the near future.

Visualization of Brain Tumors with Infrared-Labeled Aptamers for Fluorescence-Guided Surgery.

Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.

NIR-II Light-Driven Genetically Engineered Exosome Nanocatalysts for Efficient Phototherapy against Glioblastoma.

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.

Infrared laser moxibustion for cancer-related fatigue in breast cancer survivors: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. METHODS: A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. RESULTS: Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. CONCLUSION: While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

Photobiomodulation in the infrared spectrum reverses the expansion of circulating natural killer cells and brain microglial activation in Sanfilippo mice.

Sanfilippo syndrome results from inherited mutations in genes encoding lysosomal enzymes that catabolise heparan sulfate (HS), leading to early childhood-onset neurodegeneration. This study explores the therapeutic potential of photobiomodulation (PBM), which is neuroprotective and anti-inflammatory in several neurodegenerative diseases; it is also safe and PBM devices are readily available. We investigated the effects of 10-14 days transcranial PBM at 670 nm (2 or 4 J/cm2/day) or 904 nm (4 J/cm2/day) in young (3 weeks) and older (15 weeks) Sanfilippo or mucopolysaccharidosis type IIIA (MPS IIIA) mice. Although we found no PBM-induced changes in HS accumulation, astrocyte activation, CD206 (an anti-inflammatory marker) and BDNF expression in the brains of Sanfilippo mice, there was a near-normalisation of microglial activation in older MPS IIIA mice by 904 nm PBM, with decreased IBA1 expression and a return of their morphology towards a resting state. Immune cell immunophenotyping of peripheral blood with mass cytometry revealed increased pro-inflammatory signalling through pSTAT1 and p-p38 in NK and T cells in young but not older MPS IIIA mice (5 weeks of age), and expansion of NK, B and CD8+ T cells in older affected mice (17 weeks of age), highlighting the importance of innate and adaptive lymphocytes in Sanfilippo syndrome. Notably, 670 and 904 nm PBM both reversed the Sanfilippo-induced increase in pSTAT1 and p-p38 expression in multiple leukocyte populations in young mice, while 904 nm reversed the increase in NK cells in older mice. In conclusion, this is the first study to demonstrate the beneficial effects of PBM in Sanfilippo mice. The distinct reduction in microglial activation and NK cell pro-inflammatory signalling and number suggests PBM may alleviate neuroinflammation and lymphocyte activation, encouraging further investigation of PBM as a standalone, or complementary therapy in Sanfilippo syndrome.

Infrared neuromodulation-a review.

Infrared (IR) neuromodulation (INM) is an emerging light-based neuromodulation approach that can reversibly control neuronal and muscular activities through the transient and localized deposition of pulsed IR light without requiring any chemical or genetic pre-treatment of the target cells. Though the efficacy and short-term safety of INM have been widely demonstrated in both peripheral and central nervous systems, the investigations of the detailed cellular and biological processes and the underlying biophysical mechanisms are still ongoing. In this review, we discuss the current research progress in the INM field with a focus on the more recently discovered IR nerve inhibition. Major biophysical mechanisms associated with IR nerve stimulation are summarized. As the INM effects are primarily attributed to the spatiotemporal thermal transients induced by water and tissue absorption of pulsed IR light, temperature monitoring techniques and simulation models adopted in INM studies are discussed. Potential translational applications, current limitations, and challenges of the field are elucidated to provide guidance for future INM research and advancement.

Near-infrared photoimmunotherapy targeting PD-L1: Improved efficacy by preconditioning the tumor microenvironment.

Near-infrared photoimmunotherapy (NIR-PIT) is a new type of cancer therapy that employs antibody-IRDye700DX conjugates (AbPCs) and near-infrared (NIR) light at a wavelength of 689 nm, the excitation wavelength of IR700. Administered intravenously, injected AbPCs bind specifically to cells expressing the target antigen, whereupon NIR light exposure causes rapid, selective killing. This process induces an anticancer T cell response, leading to sustained anticancer host immune response. Programmed cell death ligand-1 (PD-L1) is a major inhibitory immune checkpoint molecule expressed in various cancers. In this study, we first assessed the efficacy of PD-L1-targeted NIR-PIT (αPD-L1-PIT) in immune-competent tumor mouse models. αPD-L1-PIT showed a significant therapeutic effect on the tumor models with high PD-L1 expression. Furthermore, αPD-L1-PIT induced an abscopal effect on distant tumors and long-term immunological memory. In contrast, αPD-L1-PIT was not as effective for tumor models with low PD-L1 expression. To improve the efficacy of PD-L1-targeted NIR-PIT, PEGylated interferon-gamma (IFNγ) was administered with αPD-L1-PIT. The combination therapy improved the treatment efficacy by increasing PD-L1 expression leading to more efficient cell killing by αPD-L1-PIT. Furthermore, the PEGylated IFNγ led to a CD8+ T cell-dominant tumor microenvironment (TME) with an enhanced anticancer T cell response after αPD-L1-PIT. As a result, even so-called cold tumors exhibited complete responses after αPD-L1-PIT. Thus, combination therapy of PEGylated IFNγ and PD-L1-targeted NIR-PIT has the potential to be an important future strategy for cancer immunotherapy.