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As a post transcriptional regulator of gene expression, microRNAs (miRNA) is closely related to many major human diseases, especially cancer. Therefore, its precise detection is very important for disease diagnosis and treatment. With the advancement of fluorescent dye and imaging technology, the focus has shifted from in vitro miRNA detection to in vivo miRNA imaging. This concept review summarizes signal amplification strategies including DNAzyme catalytic reaction, hybrid chain reaction (HCR), catalytic hairpin assembly (CHA) to enhance detection signal of lowly expressed miRNAs; external stimuli of ultraviolet (UV) light or near‐infrared region (NIR) light, and internal stimuli such as adenosine triphosphate (ATP), glutathione (GSH), protease and cell membrane protein to prevent nonspecific activation for the avoidance of false positive signal; and the development of fluorescent probes with emission in NIR for in vivo miRNA imaging; as well as rare earth nanoparticle based the second near‐infrared window (NIR‐II) nanoprobes with excellent tissue penetration and depth for in vivo miRNA imaging. The concept review also indicated current challenges for in vivo miRNA imaging including the dynamic monitoring of miRNA expression change and simultaneous in vivo imaging of multiple miRNAs. [ABSTRACT FROM AUTHOR]

[Display omitted] The integration of photothermal and near-infrared (NIR) imaging capabilities of indocyanine green (ICG) small molecules has attracted considerable attention in tumor diagnosis and treatment. However, the abnormal upregulation of cellular heat shock proteins (HSPs) induced by photothermal therapy (PTT) enhances cellular heat resistance, thereby severely affecting the efficacy of PTT. In this study, to address the impact of HSPs on the efficacy of PTT while obtaining high-quality NIR fluorescence imaging in the NIR region, we designed a targeted peptide@ICG nanofluorescent probe encapsulated in liposomes. The introduced cRGD targeting peptide not only possesses tumor-targeting capabilities but also features LA as the last amino acid in the targeting peptide, which can generate nitric oxide (NO) under reactive oxygen species (ROS) triggering. It can happen under 808 nm single-light source NIR light, and the guanidine group in the peptide decomposes and combines with singlet oxygen molecules to generate NO gas molecules, thereby exerting an elevated photothermal effect by inhibiting the expression of HSP70. In addition, the nanoprobes enable deep imaging and treatment of glioma in situ and can be combined with a laser speckle contrast imaging (LSCI) system for multimodal imaging. This composite probe demonstrates synergistic tumor therapeutic effects of photodynamic therapy (PDT), PTT, and gas therapy, offering a promising strategy for cancer treatment. [ABSTRACT FROM AUTHOR]

Eliciting anti-tumor immune responses and improving the tumor microenvironment crucial for boosting the effectiveness of anti-PD-1 immunotherapy. Tumor-associated macrophages (TAMs), the primary types of immune cells infiltrating tumors, play a critical role in the formation of an immunosuppressive microenvironment. In this study, we constructed a novel Evans Blue (EB)-based in vivo self-assembled nanocarrier system, mUNO-EB-ICG-Fc@Alb nanoparticles (designated as MA NPs), for targeted imaging and clearance of M2-TAMs to elicit antitumor immunotherapy of PD-1 inhibitor. In vitro experiments demonstrated the specific fluorescence imaging and killing effect of MA NPs on M2-TAMs. In vivo experiments shown that MA NPs-induced chemodynamic therapy (CDT) successfully reversed the tumor immunosuppressive microenvironment (ITM), promoted intratumoral infiltration of T lymphocytes, and ultimately enhancing the anti-tumor immunotherapy effect of PD-1 inhibitors. This study might provide good inspiration for improving the therapeutic efficacy of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Recent advances are achieved in the design and development of efficient organic photosensitizers (PSs), especially with fluorescence imaging navigation in the second near‐infrared (NIR‐II, 1000–1700 nm) region. However, there are simply a handful of NIR‐II emissive organic PSs with efficient oxygen‐independent capability due to the scarcity of high‐performance NIR‐responsive organic materials and targeted delivery. Herein, a NIR‐II‐emissive organic nanomedicine with biomimetic engineering for high‐performance NIR‐II imaging and targeted multiple phototherapies of pancreatic tumors is reported. An A‐D‐A‐type conjugated small‐molecule TPC is designed and used to prepare water‐dispersive nanoparticles, which demonstrated high efficiency for type I and type II photodynamic performances, good photothermal conversion of 57%, and bright NIR‐II emission with a quantum yield of 9.8% under 808 nm light irradiation. With pancreatic cancer cell membrane camouflage, the biomimetic TPC nanomedicine achieved high‐resolution and targeted bioimaging of whole‐body blood vessels and tumors. Antitumor experiments demonstrated the high efficiency of the biomimetic TPC nanomedicine for pancreatic tumor elimination and good biosafety with 808 nm light irradiation. This work demonstrated a NIR‐II‐emissive versatile nanomedicine with enhanced tumor‐targeting for high‐resolution NIR‐II bioimaging and superior phototheranostics, providing a feasible idea for the evolution of targeted and high‐performance theranostics. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) poses a significant and escalating medical challenge, where precise diagnosis and timely intervention hold utmost importance in halting its deterioration. Nevertheless, persistent obstacles arise from the lack of agents proficient in both real‐time diagnosis and efficient mitigation of ALI. Here, a biocatalytic and second near‐infrared (NIR‐II) fluorescence‐illuminating nanoplatform is designed to simultaneously facilitate real‐time monitoring and robust inflammation alleviation in ALI. The study first develops a new aggregation‐induced emission luminogen with trifluoromethyl substitutions, which simultaneously increase NIR‐II emission wavelength and fluorescence brightness. The molecular probe is further integrated into biocatalytic hollow ceria nanostructures, and cloaked with pre‐activated macrophage membranes for targeted inflammation intervention. Upon inhalation administration in ALI mice, the theranostic nanoagents leverage the bright NIR‐II emission and active inflammation‐tropic properties for in vivo sensitive NIR‐II imaging of ALI, which also facilitates real‐time tracking of the nanoagents' distribution and dynamic fate within pneumonia milieu. Concurrently, the catalytic prowess of the nanoplatforms efficaciously scavenges excess reactive oxygen species, dampens proinflammatory cytokines, and promotes macrophage repolarization, substantially alleviating acute lung damage. The multifaceted nanoplatform integrates NIR‐II bioimaging with nanocatalysis‐mediated immunoregulation, offering a versatile and promising approach for addressing the intricate challenges posed by acute inflammation diseases. [ABSTRACT FROM AUTHOR]

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near‐infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep‐penetrating, organelle‐targeted pyroptosis‐mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near‐infrared‐II (NIR‐II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria‐targeting abilities, and a large Stokes shift. Through nano‐precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type‐I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor‐targeting ability via NIR‐II fluorescence imaging (NIR‐II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs‐mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT. [ABSTRACT FROM AUTHOR]

The lymphatic system, alongside blood circulation, is crucial for maintaining bodily equilibrium and immune surveillance. Despite its importance, lymphatic imaging techniques lag behind those for blood circulation. Fluorescence imaging, particularly in the near-infrared-II (NIR-II) region, offers promising capabilities with centimeter-scale tissue penetration and micron-scale spatial resolution, sparking interest in visualizing the lymphatic system. Although indocyanine green (ICG) has been approved by the Food and Drug Administration (FDA) for use as a near-infrared-I (NIR-I) region fluorescent dye, its limitations include shallow penetration depth and low signal-to-noise ratio. Research suggests that ICG's fluorescence emission tail in the second near-infrared window holds potential for high-quality NIR-II imaging. However, challenges like short circulation half-life and concentration-dependent aggregation hinder its wider application. Here we developed HA@ICG nanoparticles (NPs), a superior ICG-based NIR-II fluorescent probe with excellent biocompatibility, prolonging in vivo imaging, and enhancing photostability compared to ICG alone. Leveraging LYVE-1, a prominent lymphatic endothelial cell receptor that binds specifically to hyaluronic acid (HA), our nanoprobes exhibit exceptional performance in targeting lymphatic system imaging. Moreover, our findings demonstrate the capability of HA@ICG NPs for capillary imaging, offering a means to assess local microcirculatory blood supply. These compelling results underscore the promising potential of HA@ICG NPs for achieving high-resolution bioimaging of nanomedicines in the NIR-II window. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is a mechanism by which cancer cells alter their metabolic patterns to promote cell proliferation and growth, thereby enabling their resistance to external stress. 2-Deoxy- D -glucose (2DG) can eliminate their energy source by inhibiting glucose glycolysis, leading to cancer cell death through starvation. However, a compensatory increase in mitochondrial metabolism inhibits its efficacy. Herein, we propose a synergistic approach that combines photodynamic therapy (PDT) with starvation therapy to address this challenge. To monitor the nanodrugs and determine the optimal triggering time for precise tumor therapy, a multifunctional nano-platform comprising lanthanide-doped nanoparticle (LnNP) cores was constructed and combined with mesoporous silicon shells loaded with 2DG and photosensitizer chlorin e6 (Ce6) in the mesopore channels. Under 980 nm near-infrared light excitation, the downshifted 1550 nm fluorescence signal in the second near-infrared (NIR-II, 1000–1700 nm) window from the LnNPs was used to monitor the accumulation of nanomaterials in tumors. Furthermore, upconverted 650 nm light excited the Ce6 to generate singlet oxygen for PDT, which damaged mitochondrial function and enhanced the efficacy of 2DG by inhibiting hexokinase 2 and lactate dehydrogenase A expressions. As a result, glucose metabolism reprogramming was inhibited and the efficiency of starvation therapy was significantly enhanced. Overall, the proposed NIR-II bioimaging-guided PDT-augmented starvation therapy, which simultaneously inhibited glycolysis and mitochondria, facilitated the effects of a cancer theranostic system. [ABSTRACT FROM AUTHOR]

Lower extremity peripheral artery disease (PAD) is a growing global health problem. New methods to diagnose PAD have been explored in recent years. At present, the majority of imaging methods for PAD focus on the macrovascular blood flow, and the exploration of microcirculation and tissue perfusion of PAD remains largely insufficient. In this report, we applied three new imaging technologies, i.e., second near-infrared region (NIR-II, 900–1,880 nm wavelengths) imaging, optical coherence tomography angiography (OCTA), and laser speckle flowgraphy (LSFG), in a PAD patient with a healthy human subject as control. Our results showed that the PAD patient had poorer tissue perfusion than the control without observed adverse effects. Moreover, compared with the first near-infrared region (NIR-I, 700–900 nm wavelengths) imaging results, NIR-II imaging had a higher signal-to-background ratio and resolution than NIR-I imaging and detected microvessels that were not detected by NIR-I imaging. These observations suggested that NIR-II imaging, OCTA, and LSFG are potentially safe and effective methods for diagnosing PAD.

Tumor hypoxia diminishes the effectiveness of traditional type II photodynamic therapy (PDT) due to oxygen consumption. Type I PDT, which can operate independently of oxygen, is a viable option for treating hypoxic tumors. In this study, we have designed and synthesized JSK@PEG-IR820 NPs that are responsive to the tumor microenvironment (TME) to enhance type I PDT through glutathione (GSH) depletion. Our approach aims to expand the sources of therapeutic benefits by promoting the generation of superoxide radicals (O2−.) while minimizing their consumption. The diisopropyl group within PEG-IR820 serves a dual purpose: it functions as a pH sensor for the disassembly of the NPs to release JSK and enhances intermolecular electron transfer to IR820, facilitating efficient O2−. generation. Simultaneously, the release of JSK leads to GSH depletion, resulting in the generation of nitric oxide (NO). This, in turn, contributes to the formation of highly cytotoxic peroxynitrite (ONOO−.), thereby enhancing the therapeutic efficacy of these NPs. NIR-II fluorescence imaging guided therapy has achieved successful tumor eradication with the assistance of laser therapy.

The design of nanocarriers that selectively target the liver or kidney is a significant challenge in drug delivery due to the diverse physiological structures and inherent characteristics, as well as their distinct requirements for nanocarriers. Herein, a strategy to synthesize a series of second near‐infrared region (NIR‐II) emitting gold nanocarriers for fine‐tuning liver or kidney‐specific delivery via altering their surface chemistry using cucurbit[7]uril (CB[7]) and Cys‐Arg‐Gly‐Asp (CRGD) peptide is reported. Accordingly, it shows that ultrasmall nanocarriers can facilitate kidney‐targeted delivery in cisplatin‐induced acute kidney injury (AKI) mice, which significantly boosted the accumulation of dexamethasone (DXM) loaded onto the nanocarriers at the site of injured kidneys, thereby achieving improved therapeutic results. Thus, this organ‐specific delivery strategy holds tremendous promise for improving drug delivery efficiency and providing new perspectives and methods for personalized treatments. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the gold standard for the treatment of end-stage renal diseases (ESRDs). However, the scarcity of donor kidneys has caused more and more ESRD patients to be stuck on the waiting list for transplant surgery. Improving the survival rate for renal grafts is an alternative solution to the shortage of donor kidneys. Therefore, real-time monitoring of the surgical process is crucial to the success of kidney transplantation, but efficient methods and techniques are lacking. Herein, a fluorescence technology based on bright, photostable and long-circulating aggregation-induced emission (AIE) active NIR-II nano-contrast agent DIPT-ICF nanoparticles for the whole-process monitoring and evaluation of renal transplantation has been reported. In the aggregated state, DIPT-ICF exhibits superior photophysical properties compared with the commercial dyes IR-26 and IR-1061. Besides, the long-circulating characteristic of the AIE nano-contrast agent helps to achieve renal angiography in kidney retrieval surgery, donor kidney quality evaluation, diagnosing vascular and ureteral complications, and assessment of renal graft reperfusion beyond renovascular reconstruction, which considerably outperforms the clinically approved indocyanine green (ICG). [ABSTRACT FROM AUTHOR]

Hypoxia is the common characteristic of almost all solid tumors, which prevents therapeutic drugs from reaching the tumors. Therefore, the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely concerned. As carbonic anhydrase IX (CA IX) is abundantly distributed on the hypoxia tumor cells, it is considered as a potential tumor biomarker. 4-(2-Aminoethyl)benzenesulfonamide (ABS) as a CA IX inhibitor has inherent inhibitory activity and good targeting effect. In this study, Ag2S quantum dots (QDs) were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe (Ag2S@polyethylene glycol (PEG)-ABS) through ligand exchange and amide condensation reaction. Ag2S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II (NIR-II) fluorescence characteristics of Ag2S QDs. PEG modification of Ag2S QDs greatly improves its water solubility and stability, and therefore achieves high photothermal stability and high photothermal conversion efficiency (PCE) of 45.17%. Under laser irradiation, Ag2S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells (CT-26) in vitro. It also has been proved that Ag2S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good biocompatibility. Therefore, it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3 -Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation. [ABSTRACT FROM AUTHOR]

Developing molecular fluorophores with enhanced fluorescence in aggregate state for the second near‐infrared (NIR‐II) imaging is highly desirable but remains a tremendous challenge due to the lack of reliable design guidelines. Herein, we report an aromatic substituent strategy to construct highly bright NIR‐II J‐aggregates. Introduction of electron‐withdrawing substituents at 3,5‐aryl and meso positions of classic boron dipyrromethene (BODIPY) skeleton can promote slip‐stacked J‐type arrangement and further boost NIR‐II fluorescence of J‐aggregates via increased electrostatic repulsion and intermolecular hydrogen bond interaction. Notably, NOBDP‐NO2 with three nitro groups (−NO2) shows intense NIR‐II fluorescence at 1065 nm and high absolute quantum yield of 3.21 % in solid state, which can be successfully applied in bioimaging, high‐level encoding encryption, and information storage. Moreover, guided by this electron‐withdrawing substituent strategy, other skeletons (thieno‐fused BODIPY, aza‐BODIPY, and heptamethine cyanine) modified with −NO2 are converted into J‐type aggregates with enhanced NIR‐II fluorescence, showing great potential to convert aggregation caused emission quenching (ACQ) dyes into brilliant J‐aggregates. This study provides a universal method for construction of strong NIR‐II emissive J‐aggregates by rationally manipulating molecular packing and establishing relationships among molecular structures, intermolecular interactions, and fluorescence properties. [ABSTRACT FROM AUTHOR]

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000–1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for causing life-threatening infections that result in high morbidity and mortality rates. The development of advanced imaging and therapeutic methods for in vivo diagnosis and treatment of MRSA infections remains challenging. Here, we develop a hybrid nanoplatform based on rare-earth-doped nanoparticles (RENPs) sensitized by a moiety-engineered near-infrared (NIR) TPEO-820 dye and with a ZIF-8 layer that incorporates CysNO, a photochemically triggered nitric oxide donor. We then use the hybrid for both NIR-II bioimaging and photoactivatable treatment of MRSA-infected wounds. We show that the NIR dye sensitization leads to an 8.5-fold enhancement of the downshifting emission and facilitates deep-tissue NIR-II imaging of bacterial infections. Moreover, the sensitization strategy enhances the UV emission of RENPs by two orders of magnitude, leading to the efficiently controllable release of nitric oxide for effective disinfection of MRSA in vitro and in vivo. The hybrid nanoplatform thus offers promising opportunities for simultaneous localization and controllable treatment of MRSA. Early detection and treatment of MRSA infections are crucial for reducing public health risks. It is a significant challenge that develops sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections. Herein, a nanoplatform has been developed for photoactivatable therapy of MRSA infections and deep tissue NIR-II imaging. This platform utilizes lanthanide-doped rare earth nanoparticles (RENPs) that are sensitized by a moiety-engineered near-infrared (NIR) dye TPEO-820. The TPEO-820 sensitized RENPs exhibit 5 times increase in the release of NO concentration for MRSA treatment compared to unsensitized RENPs, enabling precise therapy of MRSA infection both in vitro and in vivo. Moreover, the platform demonstrates NIR-II luminescence in vivo, allowing for sensitive imaging in deep tissue for MRSA infection. [Display omitted] [ABSTRACT FROM AUTHOR]

Near-infrared-II (NIR-II) imaging has shown great potential in medical diagnosis and surgical navigation, but developing safe, photostable, high-brightness molecular probes remains a great challenge. Due to their ultrasmall size resulting in highly efficient renal clearance, gold nanoclusters have shown great clinical potential. In this work, we systematically explored the effect of different ligands on the luminescence and bioactivity of gold nanoclusters. Our results show that gold nanoclusters protected by thioglycolic acid (TGA) and 6-mercaptohexanoic acid (MHA) exhibit the strongest fluorescence, while 3-mercaptopropionic acid (MPA)- and sodium sulfide (Na2S)-protected gold nanoclusters show the weakest NIR-II signal. Further doping showed that the Cd-doped MPA and MHA-protected gold nanoclusters exhibited enhanced fluorescence, but the cysteine (Cys)-, glutathione (GSH)-, and Na2S-protected gold nanoclusters showed fluorescence quenching after doping, indicating significant ligand selectivity. Because of the unique multi-energy structure and the large number of electronic states at the highest occupied molecular orbital energy level, MPA- and MHA-protected gold nanoclusters exhibit high stability and photostability. In addition, gold nanoclusters with different ligands exhibited different selective enzyme-mimicking activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT). Imaging in vivo showed that gold nanoclusters could accomplish reliable imaging of cerebral vasculature, hindlimb vessels, and spine as well as monitor renal clearance. The stable nanoclusters allow the time window of imaging to reach 125 min for hindlimb imaging and 270 min for spinal imaging. The gold nanoclusters exhibit a high signal-to-noise ratio of up to 11 for whole-body imaging and show efficient renal clearance and low toxicity at an injected dose of 50 mg/kg. [ABSTRACT FROM AUTHOR]

The second near‐infrared biological window two (NIR‐II, 1000–1700 nm) imaging has made remarkable achievements in fluorescence imaging of diseases. Here, this work takes advantage of the rich spectral properties of rare‐earth doped nanoparticles (RENPs) and their capability to present multiple emission peaks in different luminescence regions simultaneously; novel RENPs are synthesized that have emission peaks in the NIR‐II1000nm (1000–1300 nm) region and enhanced emission in the NIR‐IIb (1500–1700 nm) window and are named as NEU‐RENPs. These RENPs with new compositions enable a fair comparison to evaluate their imaging performance in NIR‐II1000nm and NIR‐IIb regions under the same conditions. The imaging abilities of the resulted nanoparticles in NIR‐II1000 nm and NIR‐IIb regions are investigated systematically for local blood vessels, tumor vessels, acute inflammatory vessels, arterial thrombosis, cerebrovascular inflammation, and brain injury models. The results indicate that imaging of NIR‐IIb shows higher resolution and sensitivity than that of NIR‐II1000nm, and it has a stronger ability to accurately distinguish normal and pathological tissues. Interestingly, the fuzzy image of NIR‐II1000nm reveals more information about the background structure of the target, which is difficult to be achieved in NIR‐IIb imaging. The results prove NEU‐RENPs based NIR‐IIb imaging is preferable for biomedical applications. [ABSTRACT FROM AUTHOR]

In the biomedical field, the use of fluorescence imaging in the second near‐infrared (NIR‐II) region is growing rapidly because it imparts the advantages of reduced autofluorescence and low photon scattering. The advantage of reduced scattering is that it increases penetration depth in vivo and improves imaging clarity. Herein, this work uses mesoporous silica, a biocompatible template that can be easily modified, functionalized, and loaded with drugs for use in several bioapplications. The ZnGa2O4 spinel oxide system is integrated into mesoporous silica and different concentrations of Cr3+ and Ni2+ are loaded in octahedral sites to obtain the highest emission intensity in the NIR‐II region at 1285 nm via energy transfer from Cr3+ to Ni2+. Given that only a few nanophosphor systems with emission in the NIR‐II region are available, this work attempts to establish emission in the NIR‐II and NIR‐I regions to obtain images in vivo with an increased penetration depth to 5 mm and improved clarity for bioimaging purposes. This system will open the door for biomedical research on other NIR‐II nanophosphors. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy has emerged as one of the most promising clinical techniques to treat cancer tumors. Despite its clinical application, the cancerous immunosuppressive microenvironment limits the therapeutic efficiency of the treatment. To generate a stronger immunogenic therapeutic effect, herein, a platinum complex for chemotherapy and a BODIPY photosensitizer for photodynamic therapy are encapsulated into multimodal type II immunogenic cell death (ICD) induce nanoparticles. As the platinum complex and the photosensitizer are able to induce type II ICD, an exceptionally strong immune response is observed in triple‐negative breast cancer cells. While remaining stable and therefore poorly cytotoxic in the dark, the nanomaterial is found to quickly dissociate upon exposure to near‐infrared light, causing a multimodal mechanism of action in cancer cells as well as multicellular tumor spheroids through combined chemotherapy, photodynamic therapy, and immunotherapy. The nanoparticles are found to nearly fully eradicate a triple‐negative breast cancer tumor and therefore to strongly enhance the survival of tumor‐bearing mice models using low drug and light doses. [ABSTRACT FROM AUTHOR]

We aimed to develop a new biocompatible gastrin‐releasing peptide receptor (GRPR) targeted optical probe, IRDye800‐RM26, for fluorescence image‐guided surgery (FGS) of brain malignancies in near‐infrared window II (NIR‐II) imaging. We developed a novel GRPR targeting probe using a nine‐amino‐acid bombesin antagonist analog RM26 combined with IRDye800CW, and explored the fluorescent probe according to optical properties. Fluorescence imaging characterization in NIR‐I/II region was performed in vitro and in vivo. Following simulated NIR‐II image‐guided surgery, we obtained time‐fluorescent intensity curves and time‐signal and background ratio curves. Further, we used histological sections of brain from tumor‐beating mice model to compare imaging specificity between 5‐aminolevulinic acid (5‐ALA) and IRDye800‐RM26, and evaluated biodistribution and biocompatibility. IRDye800‐RM26 had broad emission ranging from 800 to 1200 nm, showing considerable fluorescent intensity in NIR‐II region. High‐resolution NIR‐II imaging of IRDye800‐RM26 can enhance the advantages of NIR‐I imaging. Dynamic and real time fluorescence imaging in NIR‐II region showed that the probe can be used to treat brain malignancies in mice between 12 and 24 h post injection. Its specificity in targeting glioblastoma was superior to 5‐ALA. Biodistribution analysis indicated IRDye800‐RM26 excretion in the kidney and liver. Histological and blood test analyses did not reveal acute severe toxicities in mice treated with effective dose (40 μg) of the probe for NIR‐II imaging. Because of the considerable fluorescent intensity in NIR‐II region and high spatial resolution, biocompatible and excretable IRDye800‐RM26 holds great potentials for FGS, and is essential for translation into human use. [ABSTRACT FROM AUTHOR]

Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000–1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development. A liposomal vaccine for near-infrared window II fluorescence image-guided light-triggered immunization enhances the accuracy and efficacy of vaccination through the control of antigen cross-presentation and autophagy specifically in lymph nodes. [Display omitted] [ABSTRACT FROM AUTHOR]

Breast cancer has become a huge burden with continued rise of incidence and death rate worldwide. Various methods for diagnosis and therapy of breast cancer have met the challenges of lack of complete information about the tumor location and limited therapy efficacy. Although aggregation‐induced emission luminogens (AIEgens) have shown great promise for various cancer treatment applications, they may be incompetent for deep‐seated tumor diagnosis due to the limited penetration depth. Herein, we designed and prepared a radiolabeled AIEgen‐based organic photothermal agent for bimodal PET/fluorescence imaging‐guided breast tumor photothermal therapy. The prepared multifunctional nanoparticles (68Ga‐TPA‐TTINC NPs) with NIR‐II fluorescence, gamma irradiation and photothermal conversion property could be efficiently taken up by tumor cells and induce reactive oxygen species burst in vitro, further boosting the photothermal treatment of tumor in vivo. More importantly, the nanoprobe could target and clearly visualize 4T1 tumor xenografts through PET and NIR‐II fluorescence imaging with high tumor/muscle ratio up to 4.8, which provides a promising tool and solution for breast tumor theranostics. [ABSTRACT FROM AUTHOR]

Despite significant effort, a majority of heavy‐atom‐free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near‐infrared (NIR) heavy‐atom‐free photosensitizers. Based on a series of thiopyrylium‐based NIR‐II (1000–1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron‐rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)‐domain, contributing to a ≈6‐fold reduction in energy gap (ΔEST), a ≈10‐fold accelerated ISC process, and a ≈31.49‐fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD‐PEG2K lung‐targeting dots enabled real‐time NIR‐II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation. [ABSTRACT FROM AUTHOR]

Abstract Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1–π–A–D2–R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes. Graphic Abstract

Theranostics, the combination of diagnostics and therapies, has been considered as a promising strategy for clinical cancer treatment. Nonetheless, building a smart theranostic system with multifunction for different on‐demand applications still remains elusive. Herein, an easy and user‐friendly microemulsion based method is developed to modularly assemble upconversion nanoparticles (UCNPs) and Fe3O4 nanoparticles together, forming multifunctional UCNPs/Fe3O4 superparticles with highly integrated functionalities including the 808 nm excitation for real‐time NIR‐II imaging, magnetic targeting, and the upconversion luminescence upon 980 nm excitation for on‐demand photodynamic therapy (PDT). With a magnet placed nearby the tumor, in vivo NIR‐II imaging uncovers that superparticles tend to migrate toward the tumor and exhibit intense tumor accumulation, ≈6 folds higher than that without magnetic targeting 2 h after intravenous injection. NIR laser irradiation is then used to trigger PDT, obtaining an outstanding tumor elimination under magnetic tumor targeting, which shows a high potential to be applied in targeted cancer theranostics. [ABSTRACT FROM AUTHOR]

Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH‐responsive i‐motif DNA‐mediated strategy to tailor the programmable behaviors of erbium‐based rare‐earth nanoparticles (ErNPs) decorated copper doped metal‐organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i‐motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near‐infrared (NIR) photon‐activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications. [ABSTRACT FROM AUTHOR]

High quality visualization of live mammalian embryo is an important requirement for studying fetal development. Photoacoustic tomography (PAT) and optical coherence tomography (OCT) are two advanced imaging modalities that have been utilized for embryonic imaging separately. However, high contrast, multiscale, and deep tissue imaging of embryos in vivo remains challenging. Here, we demonstrate multimodal contrast-enhanced imaging of live embryos by gold nanostar-meditated near-infrared I (NIR-I) PAT and near-infrared II (NIR-II) OCT. We investigate intravenous and intravaginal administration of gold nanostars, and significant enhancement of signal, image contrast, and imaging depth are achieved for both PAT and OCT. Our findings may facilitate detailed studies of the morphological and functional changes during embryonic development. [ABSTRACT FROM AUTHOR]

Confocal laser scanning microscopy (CLSM) is expected to exhibit a better imaging performance in the second near‐infrared (NIR‐II) windows with weak tissue scattering and autofluorescence. However, the indium gallium arsenide (InGaAs) detectors currently used for imaging in the NIR‐II region are prohibitively expensive, hampering its extensive biomedical applications. In this study, a novel NIR‐II CLSM system is developed by using the inexpensive silicon photomultiplier (SiPM) that can perform the multicolor biological imaging in vivo. Using IR‐780 iodide as the contrast agent, the NIR‐II imaging capability of constructed CLSM is inspected, demonstrating a spatial resolution of 1.68 µm (close to the diffraction limit) and a fluorophore detection sensitivity as low as 100 nm. In particular, it is discovered that the multicolor imaging performance in both NIR‐I and NIR‐II windows is comparable to those from multialkali and InGaAs photomultiplier tubes. In addition, 3D NIR‐II CLSM is also conducted for in vivo imaging of the vascular structure in mouse ear and subcutaneous tumors. To the best of authors' knowledge, this is the first time that a low‐cost detector based on a SiPM has been used for microscopic imaging of trailing fluorescence signals in the NIR‐II region of an NIR fluorescent probe. [ABSTRACT FROM AUTHOR]

Rationale: The quick and accurate detection of colorectal cancer (CRC) is essential for improving the treatment efficacy and patient survival, which nevertheless remains challenging due to low specificity and sensitivity of current CRC diagnostic approaches. Therefore, providing a robust solution for real-time and accurate tumor delineation is highly desirable. Methods: We report a novel polyacrylic acid-mediated strategy to develop the endogenous hydrogen sulfide (H 2 S)-activated NIR-II probe DCNP@PB for specific visualization of CRC and image-guided tumor surgery. The stability, biocompatibility, H 2 S-responsiveness, and NIR-II imaging capability were evaluated in vitro and in vivo . Human CRC tissues were used to evaluated the performance of the DCNP@PB. Results: By exploiting the effective inner filter effect (IFE) and fluorescence resonance energy transfer (FRET) between DCNPs and PB, luminescence of DCNP@PB can be rapidly switched ON in response to H 2 S in colorectal tumor, affording high tumor-to-background ratio (TBR). Notably, H 2 S-responsive range of DCNP@PB well matches the H 2 S concentration at tumor site, thereby minimizing nonspecific activation by other sulfur-containing substances in a complicated biological environment. Such accurate H 2 S responsiveness not only benefits the differentiation between tumor and normal tissues in the mouse model, but also clearly delineates the cancerous boundaries in human tissues specimens. Conclusion: This work presents not only a promising example of H 2 S-activated NIR-II optical probe that could be intravenously injected for in vivo applications to afford reliable information and quick feedback, but also an effective strategy to design the activatable imaging probes for precise tumor diagnosis and intraoperative decision support., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The inflammatory immune microenvironment is responsible for atherosclerotic plaque erosion and rupture. Near-infrared-II (NIR-II) fluorescence imaging has the potential to continuously monitor the spatiotemporal changes in the plaque immune microenvironment. Herein, we constructed three different NIR-II probes based on benzo[1,2- c ;4,5- c ']bis[1,2,5]thiadiazole-4,7-bis(9,9-dioctyl-9 H -fluoren-2-yl)thiophene (denoted as BBT-2FT): VHPK/BBT-2FT NPs, where VHPK is a specific peptide targeting vascular cell adhesion molecule-1; iNOS/BBT-2FT NPs for modulating the polarization of M1 macrophages by inducible NO synthase (iNOS) antibodies; and Arg-1/BBT-2FT for counterbalancing the inflammatory responses of M1 macrophages. These tracers enable precise tracking of atherosclerotic plaques and M1 and M2 macrophages through NIR-II imaging. VHPK/BBT-2FT NPs can accurately trace atherosclerotic plaques at various stages. Arg-1/BBT-2FT NPs precisely located M2 macrophages in the early plaque microenvironment with upregulation of peroxisome proliferator-activated receptor γ (PPAR-γ), signal transducer and activator of transcription (STAT) 6, and ATP-binding cassette transporter A1 (ABCA1), indicating that M2 macrophage polarization is crucial for early plaque lipid clearance. Meanwhile, iNOS/BBT-2FT NPs accurately tracked M1 macrophages in the advanced plaque microenvironment. The results showed that M1 macrophage polarization induces the formation of an inflammatory microenvironment through anaerobic glycolytic metabolism and pyroptosis in the advanced hypoxic plaque microenvironment, as indicated by the upregulation of hypoxia-inducible factor 1 alpha (HIF-1α), STAT1, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), pyruvate dehydrogenase kinase 1 (PDK1), and glucose transporter 1 (GLUT-1). Combining immunological approaches with NIR-II imaging has revealed that hypoxia-induced metabolic reprogramming of macrophages is a key factor in dynamic changes in the immune microenvironment of atherosclerotic plaques. Furthermore, our strategy shows the potential for real-time diagnosis and clinical prevention of unstable plaque rupture in atherosclerosis.

Bacterial infections can pose significant health risks as they have the potential to cause a range of illnesses. These infections can spread rapidly and lead to complications if not promptly diagnosed and treated. Therefore, it is of great significance to develop a probe to selectively target and image pathogenic bacteria while simultaneously killing them, as there are currently no effective clinical solutions available. This study presents a novel approach using near-infrared carbonized polymer dots (NIR-CPDs) for simultaneous in vivo imaging and treatment of bacterial infections. The core-shell structure of the NIR-CPDs facilitates their incorporation into bacterial cell membranes, leading to an increase in fluorescence brightness and photostability. Significantly, the NIR-CPDs exhibit selective bacterial-targeting properties, specifically identifying Staphylococcus aureus (S. aureus) while sparing Escherichia coli (E. coli). Moreover, under 808 nm laser irradiation, the NIR-CPDs exhibit potent photodynamic effects by generating reactive oxygen species that target and damage bacterial membranes. In vivo experiments on infected mouse models demonstrate not only precise imaging capabilities but also significant therapeutic efficacy, with marked improvements in wound healing. The study provides the dual-functional potential of NIR-CPDs as a highly effective tool for the advancement of medical diagnostics and therapeutics in the fight against bacterial infections., (© 2024 Wiley‐VCH GmbH.)

Abstract Accurate diagnosis and effective treatment of primary liver tumors are of great significance, and optical imaging has been widely employed in clinical imaging-guided surgery for liver tumors. The second near-infrared window (NIR-II) emissive AIEgen photosensitizers have attracted a lot of attention with higher-resolution bioimaging and deeper penetration. NIR-II aggregation-induced emission-based luminogen (AIEgen) photosensitizers have better phototherapeutic effects and accuracy of the image-guided surgery/phototherapy. Herein, an NIR-II AIEgen phototheranostic dot was proposed for NIR-II imaging-guided resection surgery and phototherapy for orthotopic hepatic tumors. Compared with indocyanine green (ICG), the AIEgen dots showed bright and sharp NIR-II emission at 1250 nm, which extended to 1600 nm with high photostability. Moreover, the AIEgen dots efficiently generated reactive oxygen species (ROS) for photodynamic therapy. Investigations of orthotopic liver tumors in vitro and in vivo demonstrated that AIEgen dots could be employed both for imaging-guided tumor surgery of early-stage tumors and for ‘downstaging’ intention to reduce the size. Moreover, the therapeutic strategy induced complete inhibition of orthotopic tumors without recurrence and with few side effects. Graphical Abstract

To overcome drug resistance and improve precision theranostics for hepatocellular carcinoma (HCC), a nanoplatform with an "off/on" function for multimodality imaging (near-infrared-II (NIR-II) fluorescence imaging, magnetic resonance imaging (MRI), and photoacoustic imaging) and synergistic therapy (photodynamic therapy and ferroptosis) activated by an acidic pH in the tumor microenvironment is proposed. Although many photosensitizers with photodynamic effects have been reported, very few of them have outstanding photodynamic effect and high stability with response to endogenous stimuli capable of NIR-II imaging. Herein, a new amphiphilic photosensitizer SR780 derived from croconaine dye, was developed with satisfactory photodynamic effects and pH-responsive NIR-II imaging. Interestingly, it was deactivated by coordination with Fe3+ (SR780@Fe) and activated during their release under mild acidic condition. Ferroptosis can generate hydroxyl free radical and lipid peroxide, which aggravate the oxidative stress of tumor cells and mediate their death while depleting glutathione (GSH) to enhance photodynamic effect. In situ pH-activatable theranostic nanoplatform, SR780@Fe-PAE-GP, was thus developed by loading SR780@Fe with pH-responsive polymers, modified by a glypican-3 (GPC-3) receptor-targeting peptide. The synergistic antitumor effects were confirmed both in vitro and in vivo , and the tumor inhibition rate of the SR780@Fe-PAE-GP + L treatment group reached 98%. An in situ pH-activatable nanoplatform (SR780@Fe-PAE-GP) is developed to enhance the synergistic effect of ferroptosis and photodynamic therapy guided by "off-on" multimodal imaging for patient-derived xenograft model of hepatocellular carcinoma. [Display omitted] • A novel amphiphilic photosensitizer with pH-responsive NIR-II fluorescence and photoacoustic imaging and photodynamic effects after excitation at 808 nm was synthesized. • After the coordination of photosensitizer and Fe3+, the effect of imaging and photodynamic therapy disappeared, but it was activated in the acidic microenvironment of tumor with "OFF/ON" function. • The released Fe3+ consumed GSH while producing ferroptosis and MRI effects, further enhancing the photodynamic efficacy. • In situ pH-activatable active targeting nanoparticles have a good synergistic theranostics effect on patient-derived xenogeneic hepatocellular carcinoma models. [ABSTRACT FROM AUTHOR]

Phototheranostics that integrates real-time optical imaging and light-controlled therapy has recently emerged as a promising paradigm for cancer theranostics. Herein, a new small molecule dye DPP-BT-TPA with strong emission above 1000 nm and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4) were designed and successfully synthesized. A multifunctional phototheranostic nanoplatform was then fabricated by encapsulating them within an amphiphilic polymer. The presence of DPP-BT-TPA enabled high-resolution imaging in the second near-infrared window (NIR-II) and efficient photothermal therapy. The prodrug was cleaved by the overexpressed glutathione (GSH) in the tumor microenvironment to release the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4. Because this process can be accelerated with elevated temperature, laser-induced hyperthermia was utilized to control the drug release and enhance the therapeutic effect. Tumors in living mice were observed through NIR-II imaging after intravenous injection of the obtained nanoparticles. Improved antitumor efficacy by photothermal/chemo/antiangiogenic combination therapy was achieved with a NIR laser both in vitro and in vivo. This work provides a promising strategy for developing tumor microenvironment responsive and light-controlled theranostic platforms. Fluorescence imaging in the second near-infrared (NIR-II, 1000–1700 nm) window and near-infrared light-controlled drug release have been recognized as efficient strategies for cancer theranostics. Herein, we present a phototheranostic platform fabricated with a biocompatible NIR-II emissive dye DPP-BT-TPA and a redox-responsive prodrug camptothecin-combretastatin A4 (CPT-CA4). DPP-BT-TPA not only provides high-resolution NIR-II imaging in vivo but also enables efficient photothermal therapy. In addition, the photothermal effect largely accelerates the release of the chemotherapeutic drug CPT and the angiogenesis inhibitor CA4 in the glutathione-overexpressed tumor microenvironment. Thus, the designed phototheranostic platform can be used for NIR-II imaging-guided photothermal/chemo/antiangiogenic combination therapy for tumors with a single laser. [Display omitted] [ABSTRACT FROM AUTHOR]

To address urgent tasks in the treatment of advanced deep‐seated tumors, a 980 nm absorbing agent with aggregation‐induced emission tendency, namely TPE‐BT‐BBTD, which simultaneously possesses the longest absorption wavelength among all the reported AIE molecules is developed. The functionality of deep near‐infrared‐II fluorescence imaging (NIR‐II FLI) and outstanding photothermal performance is well‐tailored for advanced pancreatic cancer treatment. With the covalent attachment of the programmed death‐ligand 1 (αPD‐L1) antibody, αPD‐L1@TPE‐BT‐BBTD nanoparticles show precise tumor targeting and excellent immunosuppression reversal ability. Following local photothermal therapy, immunogenic tumor vaccination is induced to trigger the infiltration of cytotoxic T lymphocytes (CTLs) in tumors. With the decreased FoxP3+ Treg cells and M2‐like macrophages that are reversed by αPD‐L1, CTLs activity is further enhanced with more production of granzyme B (GrB), which much accurately leads to tumor apoptosis and effectively suppressed spontaneous metastases. Overall, αPD‐L1@TPE‐BT‐BBTD nanoparticles based NIR‐II FLI‐mediated photo‐immunotherapy is able to significantly improve the control of primary tumor and metastasis in the treatment of advanced deep‐seated tumors. [ABSTRACT FROM AUTHOR]

Heptamethine cyanines (Cy7) typically exhibit strong near-infrared (NIR) fluorescence signals when in monodisperse states, but their distinctive π-conjugated structure leads to limited solubility in aqueous solutions, ultimately resulting in inherent fluorescence self-quenching. Enhancing the fluorescence quantum yield of these agents within aqueous environments, in order to achieve high-resolution biological imaging, presents a significant challenge. Herein, a benzothiazole-based Cy7-derivative (Cy7-BTH) is developed, exhibiting unique H-aggregation properties in aqueous solutions. Bovine serum albumin (BSA) binds to Cy7-BTH (BSA@Cy7-BTH) to modulate its molecular stacking and energy transfer, boosting its fluorescence accompanied by bright NIR-II tail emission. The competitive binding alters the planarity of Cy7-BTH, restricting its intramolecular rotation, and simutaneously changes the conformation of BSA, leading to BSA@Cy7-BTH aggregation to form hierarchical-structured nanoparticles. Notably, the BSA@Cy7-BTH nanoparticles significantly enhanced photothermal response of Cy7-BTH while maintaining its controlled reactive oxygen species (ROS) generation, offering NIR-II imaging-guided surgical removal of primary tumors, and simultaneously inhibiting cancer cell metastasis by synergistic PDT/PTT dissection of metastatic tumor cells in sentinel lymph nodes (SLNs). This study provides an innovative but facile strategy for their potential clinical applications by precisely regulating the intermolecular competitive interactions of NIR theranostic agents. [Display omitted] • A molecular competition-based supramolecular strategy was proposed for high SNR imaging. • BSA binds to Cy7-BTH (BSA@Cy7-BTH) to modulate its molecular stacking and energy transfer. • BSA@Cy7-BTH offers NIR-II imaging-guided surgical removal of primary tumors. • Metastatic tumor cells in SLNs were dissected by synergistic PDT/PTT without side effects. [ABSTRACT FROM AUTHOR]

Superior QY maintains sufficient signal strength to enable NIR-II imaging with deep penetration and high resolution I in vivo i , which avoids nonradiative decay processes ([113]), and reduces quenching effects due to aggregation ([17]) and strong interactions with water molecules outside the NIR-II probes ([111]). NIR-II photoacoustic imaging of brain diseases Because of much less attenuation of ultrasonic waves and higher photothermal conversion efficiency (PCE) in biological tissues, NIR-II photoacoustic imaging has attracted attention in biomedical fields ([90]). NIR-II probes According to the emission wavelength, NIR probes can be divided into NIR-I and NIR-II probes. Keywords: brain diseases; brain tumor; cerebrovascular; NIR-II imaging; toxicity EN brain diseases brain tumor cerebrovascular NIR-II imaging toxicity 467 490 24 07/05/22 20220701 NES 220701 Introduction As one of the most important and complex organs in the human body, the brain controls our feeling, action, memory, and thoughts. Graph: Figure 1: Depth of penetration of brain tissue with different wavelengths of light and principle of NIR-II imaging ([51]; [81]; [108]).(A) From UV to NIR-II, the tissue penetration depth is gradually increased with the increasing of wavelength, and the depth of NIR-II photoacoustic is up to 7.04 mm. [Extracted from the article]

Small‐molecule‐based second near‐infrared (NIR‐II) activatable fluorescent probes can potentially provide a high target‐to‐background ratio and deep tissue penetration. However, most of the reported NIR‐II activatable small‐molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII‐HDs, a novel dye scaffold optimized for NIR‐II probe development. In particular, dye NIRII‐HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR‐II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII‐HD5 dye, we designed three target‐activatable NIR‐II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR‐II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity. [ABSTRACT FROM AUTHOR]

The cyanine fluorophores, a kind of classic organic fluorophores, are famous for their high extinction coefficient, simple synthetic route, and relatively long absorption and emission wavelengths. Moreover, the excellent biocompatibility and low toxicity in biological samples make cyanine fluorophores show excellent application value in the biomedical field, especially in Near‐Infrared II (NIR‐II) sensing and imaging. In this review, we briefly outline the history, characteristics, and current state of development of cyanine fluorophores. In particular, we described the application of cyanine fluorophores in NIR‐II sensing and imaging. We hope this review can help researchers grab the latest information in the fast‐growing field of cyanine fluorophores for NIR‐II sensing and imaging. [ABSTRACT FROM AUTHOR]

Incomplete tumor resection is the direct cause of the tumor recurrence and metastasis after surgery. Intraoperative accurate detection and elimination of microscopic residual cancer improve surgery outcomes. In this study, a powerful D1–π–A–D2–R type phototheranostic based on aggregation-induced emission (AIE)-active the second near-infrared window (NIR-II) fluorophore is designed and constructed. The prepared theranostic agent, A1 nanoparticles (NPs), simultaneously shows high absolute quantum yield (1.23%), excellent photothermal conversion efficiency (55.3%), high molar absorption coefficient and moderate singlet oxygen generation performance. In vivo experiments indicate that NIR-II fluorescence imaging of A1 NPs precisely detect microscopic residual tumor (2 mm in diameter) in the tumor bed and metastatic lymph nodes. More notably, a novel integrated strategy that achieves complete tumor eradication (no local recurrence and metastasis after surgery) is proposed. In summary, A1 NPs possess superior imaging and treatment performance, and can detect and eliminate residual tumor lesions intraoperatively. This work provides a promising technique for future clinical applications achieving improved surgical outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background To investigate the efficacy of a PLGA-based nanobody complex in photodynamic therapy (PDT) and NIR-II imaging in A549 tumor hypoxic model. Method IR1048-MZ was firstly synthesized by conjugating a nitro imidazole group to IR1048. IR1048-MZ and Cat were then encapsulated in PLGA-SH solution. Anti-EGFR-Nanobody was also expressed and purified, and finally Anti-EGFR-Nanobody@PLGA-IR1048MZ-Cat (Nb@IC-NPs) nanobody complex was obtained based on the formation of desulfide bond between PLGA-SH and Anti-EGFR-Nanobody. Size distribution and morphology were characterized by TEM and DLS. Spectrum of Nb@IC-NPs towards NTR was measured by UV and fluorescence, while the particle’s selective response was studied using fluorescence. The uptake of Nb@IC-NPs in A549 cells was observed by flow cytometry and CLSM. In the meantime, its’ catalytic ability that decomposes H2O2 both extra-and intra-cellular was observed by fluorescence and CLSM. In vitro photodynamic toxicity of Nb@IC-NPs was examined by MTT, Live/Dead Cell Staining, Flow Cytometry and Apoptosis Assay. Tumor-bearing model was constructed to observe a semi-quantitative fluorescent distribution and the possibility of NIR-II fluorescence/photoacoustic (PA) imaging. Effect of Nb@IC-NPs on enhancing A549 tumor hypoxia and expression profile of HIF-1α was investigated in the presence of NIR. An A549 tumor metastasis model was also constructed to confirm the complex’ potential to destroy primary tumor, inhibit lung metastasis, and prolong mice’ survival. Lastly, impact of Nb@IC-NPs on mice’ main organs and blood indices was observed. Results Nb@IC-NPs was successfully fabricated with good homogeneity. The fluorescent absorbance of Nb@IC-NPs showed a linear relationship with the concentration of NTR, and a higher concentration of NTR corresponded to a stronger photoacoustic signal. In addition, Nb@IC-NPs showed a stable selectivity toward NTR. Our results also suggested a high efficient uptake of Nb@IC-NPs in A549 cells, which was more efficient than IC-NPs and IR1048-MZ alone. In vitro assays confirmed the effects of Nb@IC-NPs on catalytic O2 generation even in hypoxic cells. The cell viability was upregulated with the nanocomplex at the absence of the laser, whereas it was dramatically declined with laser treatment that excited at 980 nm. Nb@IC-NPs achieved tumor hypoxia NIR-II/PA imaging through assisting A549 gathering. When NIR was applied, Nb@IC-NPs can significantly relieve A549 cellular/tumor hypoxia by generating more reactive oxygen species (ROS), which in turn helps lower the expression level of HIF-1α. In summary, Nb@IC-NPs based PDT can efficiently decimate A549 primary tumor, inhibit metastatic lung cancer, and prolong the lifespan of the mice under tolerable dosage. At last, in vivo toxicity tests of the nanocomplex showed its biosafety to the main organs and normal blood indices values. Conclusion Nb@IC-NPs improves tumor hypoxia through catalytic reaction and lowers the expression level of HIF-1α. It achieves tumor PA imaging through intensified NIR-II fluorescence signal that caused by response of the complex to the lesion’s nitroreductase (NTR). Nb@IC-NPs based PDT can efficiently kill A549 primary tumor, inhibit a lung metastasis, as well as prolong mice’ survival cycle.

Constructing J-aggregated organic dyes represents a promising strategy for obtaining biomedical second near-infrared (NIR-II) emissive materials, as they exhibit red-shifted spectroscopic properties upon assembly into nanoparticles (NPs) in aqueous environments. However, currently available NIR-II J-aggregates primarily rely on specific molecular backbones with intricate design strategies and are susceptible to fluorescence quenching during assembly. A facile approach for constructing bright NIR-II J-aggregates using prevalent donor-acceptor (D-A) molecules is still lacking. In this study, we present a facile method that transforms D-A molecules into J-aggregates by simply bending the molecule through introducing a methyl group, enabling high-performance NIR-II phototheranostics. The TAA-BT-CN molecule exhibits hypsochromic-shift absorption upon forming H-aggregated NPs, while the designed mTAA-BT-CN with a bent structure demonstrates a bathochromic shift of over 100 nm in absorption upon forming J-aggregated NPs, leading to much enhanced NIR-II emission beyond 1100 nm. With respect to its H-aggregated counterpart with the aggregation-caused quenching (ACQ) phenomenon, the J-aggregated mTAA-BT-CN NPs exhibit a 7-fold increase in NIR-II fluorescence owing to their aggregation-induced emission (AIE) property as well as efficient generation of heat and reactive oxygen species under 808 nm light excitation. Finally, the mTAA-BT-CN NPs are employed for whole-body blood vessel imaging using NIR-II technology as well as imaging-guided tumor phototherapies. This study will facilitate the flourishing advancement of J-aggregates based on prevalent D-A-type molecules.