Synthesis of D-A-type groups modified aza-BODIPY fluorescent dye encapsulated by amphiphilic polypeptide nanoparticles for NIR-II phototheranostics.

An innovative organic small molecule with a D-A structure was synthesized by connecting triphenylamine to BODIPY via a thiophene bridge. Triphenylamine and thiophene units ingeniously modulate the balance between steric hindrance and π-π interactions around the flat aza-BODIPY core. The molecule exhibits near-infrared fluorescence absorption and emits at roughly 1100 nm, featuring a significant Stokes shift. Both the molecule and its nanoparticles demonstrate high stability and achieve a remarkable 35 % photothermal conversion efficiency when conjugated with the P(OEGMA)20-P(Asp)14 copolymer. In vitro assessments show low dark toxicity and outstanding biocompatibility. Moreover, in vivo studies and photothermal therapy in mice indicate substantial tumor shrinkage and reduced recurrence, confirming its potential in cancer treatment. These results highlight the promise of this organic molecule and its nanoparticles for NIR-II imaging-guided photothermal therapy, introducing a novel approach to phototheranostic applications for cancer management.

J-aggregates of strong electron-donating groups linked Aza-BODIPY adjusting by polypeptide for NIR-II phototheranostics.

The commonly employed strategies for engineering second near-infrared (NIR-II) organic phototheranostic agents are based on expanding conjugated backbone length, strengthening donor (D)-acceptor (A) effect, or forming J-aggregates. We constructed the D-A-D' structure by incorporating strong electron-donating methoxy and tetraphenylethene (TPE) moieties on the electron-deficient Aza-BODIPY core, and simultaneously expanded the π-conjugation effect by introducing thiophene groups, to obtain a dye BDP-TPE. Next, the nanoparticles P-TPE were prepared via the assembly of BDP-TPE with amphiphilic polypeptides (mPEG2000-P(Asp)10), and successfully constructed the J-aggregates. The obtained P-TPE exhibited strong absorption and fluorescence with maxima at 808 and 1018 nm, respectively, with a conspicuous absolute quantum yield of 0.241 %. Moreover, P-TPE also showed excellent biocompatibility, and high photothermal conversion efficiency of 61.15 %, and excellent resistance to pH, long-term storage, and photobleaching. In vitro and in vivo experiments revealed that P-TPE exhibited good biocompatibility and effectively achieved NIR-II fluorescence imaging-guided PTT with complete tumor ablation under 808 nm laser irradiation. These results provided good evidence for the use of P-TPE as a NIR-II fluorescence imaging-guided PTT therapeutic agent in vivo.

Predicting in vivo therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells in models of repairing rat facial nerve defects via second near-infrared fluorescence imaging.

AIMS: To detect the therapeutic efficacy of CelTrac1000-labeled hair follicle epidermal neural crest stem cells (EPI-NCSCs) on repairing facial nerve defects by second near-infrared (NIR-II) fluorescence imaging. MATERIALS AND METHODS: Firstly, CelTrac1000-labeled EPI-NCSCs were microinjected into the acellular nerve allografts (ANAs) to bridge a 10-mm-long gap in the buccal branch of facial nerve in adult rats. Then, Celtrac1000-labeled EPI-NCSCs were detected by NIR-II fluorescence imaging system to visualize the behavior of the transplanted cells in vivo. Additionally, the effect of the transplanted EPI-NCSCs on repairing facial nerve defect was examined. KEY FINDINGS: Through 14 weeks of dynamic observation, the transplanted EPI-NCSCs survived in the ANAs in vivo after surgery. Meanwhile, the region of the NIR-II fluorescence signals was gradually limited to be consistent with the direction of the regenerative nerve segment. Furthermore, the results of functional and morphological analysis showed that the transplanted EPI-NCSCs could promote the recovery of facial paralysis and neural regeneration after injury. SIGNIFICANCE: Our research provides a novel way to track the transplanted cells in preclinical studies of cell therapy for facial paralysis, and demonstrates the therapeutic potential of EPI-NCSCs combined with ANAs in bridging rat facial nerve defects.

Tumor microenvironment-activated theranostic nanoreactor for NIR-II Photoacoustic imaging-guided tumor-specific photothermal therapy.

Theranostic agents that can be sensitively and specifically activated by the tumor microenvironment (TME) have recently attracted considerable attention. In this study, TME-activatable 3,3',5,5'-tetramethylbenzidine (TMB)-copper peroxide (CuO2)@poly(lactic-co-glycolic acid) (PLGA)@red blood cell membrane (RBCM) (TCPR) nanoparticles (NPs) for second near-infrared photoacoustic imaging-guided tumor-specific photothermal therapy were developed by co-loading CuO2 NPs and TMB into PLGA camouflaged by RBCMs. As an efficient H2O2 supplier, once exposed to a proton-rich TME, CuO2 NPs can generate H2O2 and Cu2+, which are further reduced to Cu+ by endogenous glutathione. Subsequently, the Cu+-mediated Fenton-like reaction produces cytotoxic ·OH to kill the cancer cells and induce TMB-mediated photoacoustic and photothermal effects. Combined with the RBCM modification-prolonged blood circulation, TCPR NPs display excellent specificity and efficiency in suppressing tumor growth, paving the way for more accurate, safe, and efficient cancer theranostics.

NIR-II Surface-Enhanced Raman Scattering Nanoprobes in Biomedicine: Current Impact and Future Directions.

The field of second near-infrared (NIR-II) surface-enhanced Raman scattering (SERS) nanoprobes has made commendable progress in biomedicine. This article reviews recent advances and future development of NIR-II SERS nanoprobes. It introduces the fundamental principles of SERS nanoprobes and highlights key advances in the NIR-II window, including reduced tissue attenuation, deep penetration, maximized allowable exposure, and improved photostability. The discussion of future directions includes the refinement of nanoprobe substrates, emphasizing the tailoring of optical properties of metallic SERS-active nanoprobes, and exploring non-metallic alternatives. The intricacies of designing Raman reporters for the NIR-II resonance and the potential of these reporters to advance the field are also discussed. The integration of artificial intelligence (AI) into nanoprobe design represents a cutting-edge approach to overcome current challenges. This article also examines the emergence of deep Raman techniques for through-tissue SERS detection, toward NIR-II SERS tomography. It acknowledges instrumental advancements like improved charge-coupled device sensitivity and accelerated imaging speeds. The article concludes by addressing the critical aspects of biosafety, ease of functionalization, compatibility, and the path to clinical translation. With a comprehensive overview of current achievements and future prospects, this review aims to illuminate the path for NIR-II SERS nanoprobes to innovate diagnostic and therapeutic approaches in biomedicine.

Optical evaluation of internal damage to human hair based on second near-infrared window polarization microscopy.

OBJECTIVE: Hair beauty treatments glorify human life. As a side effect, there is a risk of deteriorating the health of the hair. Optically polarized microscopy has been used for many decades to evaluate hair conditions owing to its ease of use and low operating costs. However, the low biopermeability of light hinders the observation of detailed structures inside hair. The aim of this study is to establish an evaluation technique of internal damages in a hair by utilizing a near-infrared (NIR) light with a wavelength of 1000-1600 nm, called "second NIR window". METHODS: We built a laser scanning transmission microscope system with an indium gallium arsenide detector, a 1064 nm laser source, and optical circular polarization to visualize the anisotropy characterization of keratin fibres in hair. Samples of Asian black hair before and after bleaching, after permanent-waving, after lithium bromide (LiBr) treatment, and after heating was observed. Some parameters reflecting intra-hair damage were quantitatively compared with the parameters in digitally recorded images with analytical developments. RESULTS: The light transmittance of black hair was dramatically improved by utilizing the second NIR window. Numerical analysis of circular polarization in hair quantified the internal damage in chemically or thermally treated hair and found two different types of damage. The present method enabled quantitative evaluation of the condition changes in the cortex; for example, a decrease in circular polarizability by LiBr treatment and restoration by replacing the LiBr solution with water. In addition, black speckles were observed after the heat treatment. Longer heating and wetting times increased the appearance probability and size of the speckles. According to quantitative analyses, the emergence of black spots was independent of polarizability changes, indicating that they were not pores. CONCLUSION: Circular polarization microscopy based on near-infrared optics in the second NIR window provides an effective evaluation method for quantifying intra-hair damage caused by cosmetic treatments. The present method provides noninvasive, easy, and inexpensive hair evaluation and has potential as a gold standard in hair care research/medical fields.

OBJECTIF: les soins capillaires glorifient la vie humaine. Comme effet secondaire, il existe un risque de détérioration de la santé du cheveu. La microscopie en lumière polarisée est utilisée depuis de nombreuses décennies pour évaluer la santé capillaire en raison de sa facilité d'utilisation et de son faible coût d'exploitation. Cependant, la faible bioperméabilité de la lumière empêche l'observation des structures détaillées à l'intérieur du cheveu. Pour résoudre ce problème, cette étude tente d'établir une technique d'évaluation des atteintes internes d'un cheveu en utilisant une lumière proche infrarouge (NIR) d'une longueur d'onde de 1000 à 1600 nm, appelée « deuxième fenêtre NIR ¼. MÉTHODES: nous avons construit un système de microscope de transmission à balayage laser équipé d'un capteur indium gallium arsenide, d'une source laser de 1064 nm et d'une polarisation circulaire optique pour visualiser la caractérisation de l'anisotropie des fibres de kératine dans les cheveux. Des échantillons de cheveux noirs asiatiques ont subi un traitement avant et après la décoloration, l'ondulation permanente, le bromure de lithium (LiBr) et la chaleur. Certains paramètres reflétant les dommages intra­cheveu ont été comparés quantitativement aux paramètres des images enregistrées numériquement avec des développements analytiques. RÉSULTATS: la transmission de la lumière des cheveux noirs a été considérablement améliorée en utilisant la deuxième fenêtre NIR. L'analyse numérique de la polarisation circulaire des cheveux a quantifié les dommages internes des cheveux traités chimiquement ou thermiquement et a mis en évidence deux types de dommages différents. La présente méthode a permis d'évaluer quantitativement les changements de condition dans le cortex; par exemple, une diminution de la polarisation circulaire par le traitement par LiBr et la restauration en remplaçant la solution LiBr par de l'eau. En outre, des taches noires ont été observées après le traitement thermique. Des temps de chauffage et de mouillage plus longs ont augmenté la fréquence d'apparition et la taille des taches. D'après des analyses quantitatives, l'émergence de points noirs était indépendante des changements de polarisation, indiquant qu'il ne s'agissait pas de pores. CONCLUSION: La microscopie par polarisation circulaire basée sur l'optique proche infrarouge dans la deuxième fenêtre NIR fournit une méthode d'évaluation efficace pour quantifier les dommages intra­cheveu causés par les traitements cosmétiques. La présente méthode fournit une évaluation des cheveux non invasive, facile et peu coûteuse et a un potentiel de référence dans la recherche sur les soins capillaires/les domaines médicaux.

Rare Earth Nanoprobes for Targeted Delineation of Triple Negative Breast Cancer and Enhancement of Radioimmunotherapy.

Radiotherapy demonstrates a synergistic effect with immunotherapy by inducing a transformation of "immune cold" tumors into "immune hot" tumors in triple negative breast cancer (TNBC). Nevertheless, the effectiveness of immunotherapy is constrained by low expression of tumor-exposed antigens, inadequate inflammation, and insufficient tumor infiltrating lymphocyte (TILs). To address this predicament, novel lutecium-based rare earth nanoparticles (RENPs) are synthesized with the aim of amplifying radiation effect and tumor immune response. The nanoprobe is characterized by neodymium-based down-conversion fluorescence, demonstrating robust photostability, biocompatibility, and targetability. The conjugation of RENPs with a CXCR4 targeted drug enables precise delineation of breast tumors using a near-infrared imaging system and improves radiation efficacy via lutetium-based radio-sensitizer in vivo. Furthermore, the study shows a notable enhancement of immune response through the induction of immunogenic cell death and recruitment of TILs, resulting in the inhibition of tumor progression both in vitro and in vivo models following the administration of nanoparticles. Hence, the novel multifunctional nanoprobes incorporating various lanthanide elements offer the potential for imaging-guided tumor delineation, radio-sensitization, and immune activation post-radiation, thus presenting an efficient radio-immunotherapeutic approach for TNBC.

A Cyanine with 83.2% Photothermal Conversion Efficiency and Absorption Wavelengths over 1200 nm for Photothermal Therapy.

Developing small-molecule photothermal agents (PTAs) with good near-infrared-II (NIR-II) response for deeper tissue penetration and minimizing damage to healthy tissues has attracted much attention in photothermal therapy (PTT). However, concentrating ultra-long excitation wavelengths and high photothermal conversion efficiencies (PCEs) into a single organic small molecule is still challenging due to the lack of suitable molecular structures. Here, six polymethine cyanine molecules based on the structure of indocyanine green are synthesized by increasing the conjugated structure of the two-terminal indole salts and the number of rigid methine units, and incorporating longer alkyl side chains into the indole salts. Ultimately, IC-1224 is obtained with an absorption wavelength of more than 1200 nm, which has a high PCE up to 83.2% in the NIR-II window and exhibits excellent PTT tumor ablation performance. This provides a high-performance NIR-II-responsive PTA, and offers further possibilities for the application of PTT in biomedical fields.

Lanthanide-dye hybrid luminophores for advanced NIR-II bioimaging.

In vivo luminescence imaging in the second near-infrared window (NIR-II, 1000-2000 nm) is a potent technique for observing deep-tissue life activities, leveraging reduced light scattering, minimized autofluorescence, and moderate absorption attenuation to substantially enhance image contrast. Pushing the frontiers of NIR-II luminescence imaging forward, moving from static to dynamic event visualization, monochromatic to multicolor images, and fundamental research to clinical applications, necessitates the development of novel luminophores featuring bright emission, extendable wavelength, and optimal biocompatibility. Recently, lanthanide-dye hybrid luminophores (LDHLs) are gaining increasing attention for their wavelength extensibility, molecular size, narrowband emission, mega stokes shift, long lifetime, and high photostability. In this review, we will summarize the recent advances of NIR-II LDHLs and their applications in imaging and analysis of living mammals, and discuss future challenges in designing new LDHLs for deep-tissue imaging.

Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.

Enhancing surgical outcomes: accurate identification and removal of prostate cancer with B7-H3-targeted NIR-II molecular imaging.

PURPOSE: One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa. This study aims to construct a new NIR-II probe targeting B7-H3 (AbB7-H3-800CW) for accurate intraoperative identification and resection of PCa. METHODS: Based on the differential expression of B7-H3 in PCa, we designed a novel imaging probe to accurately identify and guide the resection of preclinical PCa models and ex vivo human PCa tissues using NIR-II fluorescence imaging technology. RESULTS: Analyzing tissue samples from 60 clinical cases of PCa, along with benign prostatic hyperplasia and normal prostate tissue from 22 cases, we observed a significant difference in B7-H3 protein expression levels (P < 0.001). Subcutaneous and orthotopic mouse models of PCa were imaged using NIR-II fluorescence after AbB7-H3-800CW injection, showing promising results with successful tumor targeting and high-contrast images achieved within 24-48 h post-injection. The imaging also enabled the detection of occult PCa lesions approximately 1 mm in diameter. In addition, imaging analysis of human PCa and adjacent tissues using AbB7-H3-800CW incubation revealed that cancer tissues exhibited a significantly higher fluorescence intensity than adjacent tissues (P < 0.05), which was conducive to the evaluation of tumor resection margin in vitro. CONCLUSION: The findings revealed that B7-H3 was a compelling imaging target for PCa. The AbB7-H3-800CW molecular imaging probe is capable of accurately identifying PCa lesions and guiding their removal. This approach can potentially reduce the rate of surgical margins under NIR-II fluorescence guidance.

NIR-II Fluorescence Sensor Based on Steric Hindrance Regulated Molecular Packing for In Vivo Epilepsy Visualization.

Fluorescence sensing is crucial to studying biological processes and diagnosing diseases, especially in the second near-infrared (NIR-II) window with reduced background signals. However, it's still a great challenge to construct "off-on" sensors when the sensing wavelength extends into the NIR-II region to obtain higher imaging contrast, mainly due to the difficult synthesis of spectral overlapped quencher. Here, we present a new fluorescence quenching strategy, which utilizes steric hindrance quencher (SHQ) to tune the molecular packing state of fluorophores and suppress the emission signal. Density functional theory (DFT) calculations further reveal that large SHQs can competitively pack with fluorophores and prevent their self-aggregation. Based on this quenching mechanism, a novel activatable "off-on" sensing method is achieved via bio-analyte responsive invalidation of SHQ, namely the Steric Hindrance Invalidation geNerated Emission (SHINE) strategy. As a proof of concept, the ClO--sensitive SHQ lead to the bright NIR-II signal release in epileptic mouse hippocampus under the skull and high photon scattering brain tissue, providing the real-time visualization of ClO- generation process in living epileptic mice.

Molecular Engineering of Activatable NIR-II Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Inflammatory Bowel Disease.

Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.

20π-Electron Antiaromatic Benziphthalocyanines with Absorption Reaching the Near-Infrared-II Region.

Although second near-infrared (NIR-II, 1000-1500 nm) light has attracted considerable attention, especially for life sciences applications, the development of organic dyes with NIR-II absorption remains a formidable challenge. Herein we report the design, synthesis, and electronic properties of 20π-electron antiaromatic benziphthalocyanines (BPcs) that exhibit intense absorption bands in the NIR region. The strong, low-energy absorption of the antiaromatic BPcs is attributed to electric-dipole-allowed HOMO-LUMO transitions with narrow band gaps, enabled by the reduced structural symmetry of BPc compared with regular porphyrins and phthalocyanines. The combination of peripheral substituents and a central metal decreases the HOMO-LUMO energy gaps, leading to the extension of the absorption bands into the NIR-II region (reaching 1100 nm) under reductive conditions.

Second near-infrared fluorescent Metal-Organic framework sensors for in vivo extracellular adenosine triphosphate monitoring.

Plant nanobionic sensors enable real-time monitoring of signaling molecules in plants by interfacing them with specifically designed nanoprobes, which have been acknowledged as species-independent analytical tools. In this study, we developed a plant nanobionic sensor for in vivo detection of extracellular adenosine triphosphate (eATP) in living plants by designing a novel second near-infrared (NIR-II) fluorescent metal-organic framework (MOF) nanoprobe. The NIR-II fluorescent nanoprobe (IR-1061 micelle@ZIF-90) with a sandwich structure was synthesized by successive encapsulation of the hydrophobic NIR-II dye IR-1061 with the amphipathic polymer DSPE-mPEG 2000 and MOF ZIF-90. Interestingly, coating ZIF-90 around IR-1061 micelles increased the NIR-II fluorescence 16.6-fold. Utilizing the ultrahigh NIR-II fluorescent emission of the designed nanoprobes and specific recognition of ZIF-90 to ATP, the nanoprobes were applied to spatial and temporal monitoring eATP in model and non-model plants under environmental stress.

A Novel Activatable Nanoradiosensitizer for Second Near-Infrared Fluorescence Imaging-Guided Safe-Dose Synergetic Chemo-Radiotherapy of Rheumatoid Arthritis.

The precise theranostics of rheumatoid arthritis (RA) remains a formidable challenge in clinical practice. Exploring novel applications of contemporary therapeutic approaches like chemo-radiotherapy is promising as a highly effective strategy for RA. Herein, a novel activatable nanoradiosensitizer-40 (denoted as IRnR-40) is developed, based on encapsulating the clinically approved drugs cisplatin (DDP) and indocyanine green (ICG) within a gelatin shell to achieve second near-infrared fluorescence (NIR-II FL) imaging-guided safe-dose synergetic chemo-radiotherapy. The high concentration of matrix metalloproteinase-9 (MMP-9) in the RA microenvironment plays a pivotal role in triggering the responsive degradation of IRnR-40, leading to the rapid release of functional molecules DDP and ICG. The released ICG serves the dual purpose of illuminating the inflamed joints to facilitate accurate target volume delineation for guiding radiotherapy, as well as acting as a real-time reporter for quantifying the release of DDP to monitor efficacy. Meanwhile, the released DDP achieves highly effective synergistic chemotherapy and radiosensitization for RA via the dual reactive oxygen species (ROS)-mediated mitochondrial apoptotic pathway. To sum up, this activatable nanoradiosensitizer IRnR-40 is believed to be the first attempt to achieve efficient NIR-II FL imaging-guided safe-dose chemo-radiotherapy for RA, which provides a new paradigm for precise theranostics of refractory benign diseases.

Oxygen Vacancy Defect Enhanced NIR-II Photothermal Performance of BiOxCl Nanosheets for Combined Phototherapy of Cancer Guided by Multimodal Imaging.

Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.

Recent Advances on NIR-II Light-Enhanced Chemodynamic Therapy.

Chemodynamic therapy (CDT) is a particular oncological therapeutic strategy by generates the highly toxic hydroxyl radical (•OH) from the dismutation of endogenous hydrogen peroxide (H2O2) via Fenton or Fenton-like reactions. However, single CDT therapies have been limited by unsatisfactory efficacy. Enhanced chemodynamic therapy (ECDT) triggered by near-infrared (NIR) is a novel therapeutic modality based on light energy to improve the efficiency of Fenton or Fenton-like reactions. However, the limited penetration and imaging capability of the visible (400-650 nm) and traditional NIR-I region (650-900 nm) light-amplified CDT restrict the prospects for its clinical application. Combined with the high penetration/high precision imaging characteristics of the second near-infrared (NIR-II,) nanoplatform, it is expected to kill deep tumors efficiently while imaging the treatment process in real-time, and more notably, the NIR-II region radiation with wavelengths above 1000 nm can minimize the irradiation damage to normal tissues. Such NIR-II ECDT nanoplatforms have greatly improved the effectiveness of CDT therapy and demonstrated extraordinary potential for clinical applications. Accordingly, various strategies have been explored in the past years to improve the efficiency of NIR-II Enhanced CDT. In this review, the mechanisms and strategies used to improve the performance of NIR-II-enhanced CDT are outlined.

Hollow Cavity CaO2 @Polydopamine Nanocomposites for pH-Responsive Ca2+ -Enhanced Efficient Mild Hyperthermia in the NIR-II Region.

Second near-infrared (NIR-II) mild photothermal therapy with higher tissue penetration depth and less damage to healthy tissues is emerging as an attractive antitumor modality, but its therapeutic efficiency is dramatically suppressed by the resistance of heat shock proteins (HSPs). As a widely explored photothermal agent, the application of polydopamine (PDA) in the NIR-II region is hampered by low photothermal conversion efficiency (PCE). Herein, its PCE in the NIR-II region is improved by developing novel hollow cavity CaO2 @PDA nanocomposites through chelation-induced diffusion of inner core Ca2+ to the shell PDA to facilitate multiple reflections of laser in the cavity. Upon pH-responsive degradation of CaO2 , its structure is transformed into a stacked "nano-mesh" with excellent light absorption and an enlarged effective irradiation area. Overloading of Ca2+ ions not only induces downregulation of HSPs but also enhances interference of light on membrane potential, which further aggravate mitochondrial dysfunction and reduce the thermotolerance of tumor cells, promoting efficient mild hyperthermia of PDA in the NIR-II region.

J-Aggregation Strategy toward Potentiated NIR-II Fluorescence Bioimaging of Molecular Fluorophores.

Molecular fluorophores emitting in the second near-infrared (NIR-II, 1000-1700 nm) window with strong optical harvesting and high quantum yields hold great potential for in vivo deep-tissue bioimaging and high-resolution biosensing. Recently, J-aggregates are harnessed to engineer long-wavelength NIR-II emitters and show unique superiority in tumor detection, vessel mapping, surgical navigation, and phototheranostics due to their bathochromic-shifted optical bands in the required slip-stacked arrangement aggregation state. However, despite the preliminary progress of NIR-II J-aggregates and theoretical study of structure-property relationships, further paradigms of NIR-II J-aggregates remain scarce due to the lack of study on aggregated fluorophores with slip-stacked fashion. In this effort, how to utilize the specific molecular structure to form slip-stacked packing motifs with J-type aggregated exciton coupling is emphatically elucidated. First, several molecular regulating strategies to achieve NIR-II J-aggregates containing intermolecular interactions and external conditions are positively summarized and deeply analyzed. Then, the recent reports on J-aggregates for NIR-II bioimaging and theranostics are systematically summarized to provide a clear reference and direction for promoting the development of NIR-II organic fluorophores. Eventually, the prospective efforts on ameliorating and promoting NIR-II J-aggregates to further clinical practices are outlined.