Enlarging the Reservoir: High Absorption Coefficient Dyes Enable Synergetic Near Infrared-II Fluorescence Imaging and Near Infrared-I Photothermal Therapy

Although organic materials with near infrared (NIR)-II fluorescence and a photothermal effect have been widely investigated for the accurate diagnosis and treatment of tumors, optimizing the output signals of both remain challenging. Here, a strategy by “enlarging absorption reservoir” to address this issue, since an increase in photon absorption can naturally enhance output signals, is proposed. As a proof-of-concept, a large π-conjugated diketopyrrolopyrrole (DPP) unit is selected to fabricate strong light-absorbing systems. To enhance solid-state fluorescence, highly twisted alkylthiophene–benzobisthiadiazole–alkylthiophene and triphenylamine rotor are introduced to restrict the strong intermolecular π–π interactions. Moreover, the number of DPP units in molecules is engineered to optimize photophysical properties. Results show that TDADT with two DPP units possesses an exceptionally high molar absorptivity of 2.1 × 10⁵ L mol⁻¹ cm⁻¹ at 808 nm, an acceptable NIR-II quantum yield of 0.1% (emission peak at 1270 nm), and a sizeable photothermal conversion efficiency of 60.4%. The excellent photophysical properties of the TDADT nanoparticles are particularly suitable for in vivo NIR-II imaging-guided cancer surgery and NIR-I photothermal therapy. The presented strategy provides a new approach of designing highly efficient NIR-II phototheranostic agents.     

Precise Molecular Engineering of Photosensitizers with Aggregation‐Induced Emission over 800 nm for Photodynamic Therapy

Owing to efficient singlet oxygen (¹O₂) generation in aggregate state, photosensitizers (PSs) with aggregation‐induced emission (AIE) have attracted much research interests in photodynamic therapy (PDT). In addition to high ¹O₂ generation efficiency, strong molar absorption in long‐wavelength range and near‐infrared (NIR) emission are also highly desirable, but difficult to achieve for AIE PSs since the twisted structures in AIE moieties usually lead to absorption and emission in short‐wavelength range. In this contribution, through acceptor engineering, a new AIE PS of TBT is designed to show aggregation‐induced NIR emission centered at 810 nm, broad absorption in the range between 300 and 700 nm with a large molar absorption coefficient and a high ¹O₂ generation efficiency under white light irradiation. Further, donor engineering by attaching two branched flexible chains to TBT yielded TBTC8 , which circumvented the strong intermolecular interactions of TBT in nanoparticles (NPs), yielding TBTC8 NPs with optimized overall performance in ¹O₂ generation, absorption, and emission. Subsequent PDT results in both in vitro and in vivo studies indicate that TBTC8 NPs are promising candidates in practical application.     

Activatable NIR-II Lanthanides-Polymetallic Oxomolybdate Hybrid Nanosensors for Monitoring Chemotherapy Induced Enteritis

Chemotherapy-induced enteritis is one of the side effects associated with cancer therapy, which significantly affects the treatment effect, but there is no effective clinical detection method that can early diagnose its occurrence and progression. Here, a series of second near-infrared window (NIR-II) hybrid nanosensors are designed that consisted of lanthanide nanoparticles and β-Mo2C-derived polymetallic oxomolybdate nanoclusters (Ln@POM). Based on the high sensitivity of POM to reactive oxygen species (ROS) closely related to chemotherapy-induced enteritis, the NIR-II luminescence intensity and lifetime of Ln@POM (Ln: Yb³⁺, Nd³⁺, Ho³⁺, Tm³⁺, Er³⁺) show excellent responsiveness to H₂O₂ and HClO with the detection limit down to 0.15 and 0.14 µm , respectively. Utilizing Nd@POM as a ROS-activated NIR-II nanosensor, the chemotherapeutic enteritis is successfully detected within 7 h after induction of chemotherapy drugs, which is significantly earlier than the gold standard method (immunohistochemistry, 24 h). These results demonstrate that the designed hybrid nanosensors are promising optical tools for the early diagnosis of ROS-related diseases.     

Dye-Sensitized Downconversion Nanoprobes with Emission Beyond 1500 nm for Ratiometric Visualization of Cancer Redox State

Detection of glutathione (GSH) in the body is essential to accurately map the redox state of cells and real-time visualization of physiological and pathological conditions in vivo. However, traditional fluorescence (FL) imaging in the near-infrared I region (NIR-I, 650–900 nm) is difficult to quantitively visualize GSH in vivo due to the tissue autofluorescence background and disastrous photon scattering. Herein, a NIR-II_b (1500–1700 nm) nanoprobe consisting of 4-nitrophenol-Cy7 (NPh) conjugated lanthanide-based downconversion nanoparticles (DCNP@NPh-PEG) is developed for in vivo ratiometric imaging of GSH. In the presence of GSH, NPh shows responsively enhanced FL emission at 808 nm, thus enhancing FL signal at 1550 nm of DCNPs excited by 808 nm (F_{1550, 808Ex}) through non-radiative energy transfer (NRET) effect, while the fluorescence of DCNP at 1550 nm excited by 980 nm laser (F_{1550, 980Ex}) is stable because no NRET occurred. The ratiometric F_{1550, 980Ex}/F_{1550, 808Ex} value exhibits a linearship with GSH concentration ranged from 0–24 mm with detection limit of 0.3 mm . The NIR-II_b nanoprobe has excellent performance in detecting and imaging GSH in both subcutaneous tumor and orthotopic colon tumor in vivo with high accuracy and resolution. The design strategy of the ratiometric NIR-II FL nanoprobe based on the activated FERT effect provides a reliable tool for the development of NIR-II nanoprobes for accurate biosensing in vivo.     

NIR-II Responsive Inorganic 2D Nanomaterials for Cancer Photothermal Therapy: Recent Advances and Future Challenges

Non-invasive cancer photothermal therapy (PTT) is a promising replacement for traditional cancer treatments. The second near-infrared region induced PTT (NIR-II PTT, 1000–1500 nm) with less energy dissipation has been developed for deeper-seated tumor treatment in recent years compared with the traditional first near-infrared light (750–1000 nm). In addition, the use of emerging inorganic 2D nanomaterials as photothermal agents (PTAs) further enhanced PTT efficiency due to their intrinsic photothermal properties. NIR-II light stimulated inorganic 2D nanomaterials for PTT is becoming a hot topic in both academic and clinical fields. This review summarizes the categories, structures, and photothermal conversion properties of inorganic 2D nanomaterials for the first time. The recent synergistic strategies of NIR-II responsive PTT combined with other treatment approaches including chemotherapy, chemodynamic therapy, photodynamic therapy, radiotherapy are summarized. The future challenges and perspectives on these 2D nanomaterials for NIR-II responsive PTT systems construction are further discussed.     

Molecular Engineering of NIR-II AIE Luminogen Excited at 1700 nm for Ultradeep Intravital Brain Two-Photon Fluorescence Imaging

The limited tissue penetration depth and spatial resolution are the major bottlenecks for deep-brain imaging. In this study, molecular engineering by tailoring electron donors is conducted to develop for the first time an NIR-II (second near-infrared) emissive fluorescence probe, namely DCTBT, for effective deep-brain two-photon fluorescence imaging. Benefiting from its good biocompatibility, high photostability, bright NIR-II emission as aggregates and large two-photon fluorescence action cross section at the 1700 nm excitation window, DCTBT offers the imaging depths of 2180 and 1135 µm in mouse brain with removed and intact skull, respectively. These results are the record depths for brain imaging, compared to all kinds of fluorescent probes and all modalities of multiphoton microscopy at all demonstrated excitation wavelengths. Moreover, with DCTBT labeling, hemodynamic imaging of blood flow in mouse brain vessels down to a depth of 714 µm with the intact skull is achieved. Multiphoton fluorescence imaging with the NIR-II probe DCTBT excited at the 1700 nm window may readily provide methodology for deep-brain structural and hemodynamic research.     

Highly efficient near-infrared emission from binuclear cyclo-metalated platinum complexes bridged with 5-(4-octyloxyphenyl)-1,3,4-oxadiazole-2-thiol in PLEDs

A novel near-infrared-emitting binuclear platinum complex of (piq)₂Pt₂(μ-C₈OXT)₂ was synthesized and characterized, in which piq is 1-phenylisoquinolinato and C₈OXT is a bridging ancillary ligand of 5-(4-octyloxyphenyl)-1,3,4-oxadiazole)-2-thiol. Its optophysical, electrochemical and electroluminescent characteristics were primary studied. This binuclear platinum complex exhibited an intense UV absorption at about 493 nm from the metal–metal-to-ligand charge transfer transition and a bright near-infrared emission at 721 nm in chloromethane. Using (piq)₂Pt₂(μ-C₈OXT)₂ as a single dopant, its single-emissive-layer polymer light-emitting devices presented a high-efficiency near-infrared emission peaked at 702 nm with the maximum external quantum efficiency of 6.3% at 7.6 mA cm^?2. This work provides an efficient approach to realize high-efficiency near-infrared emission by binuclear platinum complexes.     

Remarkable Suppression of Vibrational Relaxation in Organic Semiconducting Polymers by Introducing a Weak Electron Donor for Improved NIR-II Phototheranostics

Exploration of high-efficiency agents for near-infrared-II fluorescence imaging (NIR-II FI) promotes the development of NIR-II FI in life science. Despite the extensive use of organic semiconducting nanomaterials for NIR-II FI, the fluorescence efficiency is barely satisfying, and the molecular guideline to improve the imaging quality has not been clarified yet. This contribution designs self-brightened organic semiconducting polymers (OSPs) for improved NIR-II phototheranostics of cancer. The amplification of NIR-II brightness is realized by incorporating a weak electron-donating unit (5,5′-dibromo-4,4′-didodecyl-2,2′-bithiophene, DDB) into the semiconducting backbone with strong electron donor–acceptor alternated structure, which exhibits 6.3-fold and 25-fold fluorescence enhancement compared with the counterpart OSP at the same optical concentration and mass concentration, respectively. The broadband femtosecond transient absorption spectra experimentally elucidate the DDB doping-induced suppression of vibrational relaxation as the underlying reason for the NIR-II fluorescence amplification. Biocompatible nanoparticles fabricated from the optimal OSP₁₂ exhibit excellent NIR-II phototheranostic performance both in vitro and in vivo. Our research not only reveals the mechanistic insights for fluorescence enhancement of the designed OSPs from the essential view but also highlights an effective molecular methodology to guide the rational design of imaging agents with enhanced NIR-II brightness for improved phototheranostics in living subjects.     

High thermal annealing effect on structural and optical properties of ZnO–SiO2 nanocomposite

The effect of annealing temperature on photoluminescence (PL) of ZnO–SiO₂ nanocomposite was investigated. The ZnO–SiO₂ nanocomposite was annealed at different temperatures from 600 °C to 1000 °C with a step of 100 °C. High Resolution Transmission Electron Microscope (HR-TEM) pictures showed ZnO nanoparticles of 5 nm are capped with amorphous SiO₂ matrix. Field Emission Scanning Electron Microscope (FE-SEM) pictures showed that samples exhibit spherical morphology up to 800 °C and dumbbell morphology above 800 °C. The absorption spectrum of ZnO–SiO₂ nanocomposite suffers a blue-shift from 369 nm to 365 nm with increase of temperature from 800 °C to 1000 °C. The PL spectrum of ZnO–SiO₂ nanocomposite exhibited an UV emission positioned at 396 nm. The UV emission intensity increased as the temperature increased from 600 °C to 700 °C and then decreased for samples annealed at and above 800^°C. The XRD results showed that formation of willemite phase starts at 800 °C and pure willemite phase formed at 1000 °C. The decrease of the intensity of 396 nm emission peak at 900 °C and 1000 °C is due to the collapse of the ZnO hexagonal structure. This is due to the dominant diffusion of Zn into SiO₂ at these temperatures. At 1000 °C, an emission peak at 388 nm is observed in addition to UV emission of ZnO at 396 nm and is believed to be originated from the willemite.     

Molecular Engineering of Efficient Singlet Oxygen Generators with Near-Infrared AIE Features for Mitochondrial Targeted Photodynamic Therapy

Aggregation-caused fluorescence quenching with insufficient production of reactive oxygen species (ROS) has limited the application of photosensitizers (PSs) in fluorescence-imaging-guided photodynamic therapy (PDT). Aggregation-induced emission PSs (AIE-PSs) exhibit enhanced fluorescence intensity and a high efficiency of ROS generation in the aggregation state, which provides an opportunity to solve the above problems. Herein, a series of AIE-PSs are successfully designed and synthesized by adjusting the D–A intensity through molecular engineering. The photophysical properties and theoretical calculations prove that the synergistic effect of 3,4-ethylenedioxythiophene and quinolinium increases the intramolecular charge transfer effect (ICT) of the whole molecule and promotes the intersystem crossing (ISC) from the lowest excited singlet state (S₁) to the lowest triplet state (T₁). Among these AIE-PSs, the optimal AIE-PS (TPA-DT-Qy) exhibits the highest generation yield of ¹O₂ (5.3-fold of Rose Bengal). Further PDT experiments show that the TPA-DT-Qy has a highly efficient photodynamic ablation of breast cancer cells (MCF-7 and MDA-MB-231) under white light irradiation. Moreover, the photodynamic antibacterial study indicates that TPA-DT-Qy has the discrimination and excellent photodynamic inactivation of S. aureus. This work provides a feasible strategy for the molecular engineering of novel AIE-PSs to improve the development of fluorescence-imaging-guided PDT.     

Giant Red-Shifted Emission in (Sr,Ba)Y2O4:Eu2+ Phosphor Toward Broadband Near-Infrared Luminescence

Near-infrared (NIR) light-emitting diodes (LEDs) light sources are desirable in photonic, optoelectronic, and biological applications. However, developing broadband red and NIR-emitting phosphors with good thermal stability is always a challenge. Herein, the synthesis of Eu²⁺-activated SrY₂O₄ red phosphor with high photoluminescence quantum efficiency and broad emission band ranging from 540 to 770 nm and peaking at 620 nm under 450 nm excitation is designed. Sr/Ba substitution in SrY₂O₄:Eu²⁺ has been further utilized to achieve tunable emission by modifying the local environment, which facilitates the giant red-shifted emission from 620 to 773 nm while maintaining the outstanding thermal stability of SrY₂O₄:Eu²⁺. The NIR emission is attributed to the enhanced Stokes shift and crystal field strength originated from the local structural distortions of [Y1/Eu1O₆] and [Y2/Eu2O₆]. The investigation in charge distribution around Y/Eu provides additional insight into increasing covalency to tune the emission toward the NIR region. As-fabricated NIR phosphor-converted LEDs demonstration shows its potential in night-vision technologies. This study reveals the NIR luminescence mechanism of Eu²⁺ in oxide-based hosts and provides a design principle for exploiting Eu²⁺-doped NIR phosphors with good thermal stability.     

Renal-Clearable Nickel-Doped Carbon Dots with Boosted Photothermal Conversion Efficiency for Multimodal Imaging-Guided Cancer Therapy in the Second Near-Infrared Biowindow

Photothermal agents with absorption in the second near-infrared (NIR-II) biowindow have attracted increasing attention for photothermal therapy (PTT) on account of their deeper tissue penetration capacity. However, most of the current NIR-II photothermal agents exhibit low photothermal conversion efficiency (PCE) and long-term biotoxicity. To overcome these shortcomings, herein, nickel and nitrogen co-doped carbon dots (Ni-CDs, ≈4.6 nm) are prepared via a facile one-pot hydrothermal approach for imaging-guided PTT in the NIR-II window. The Ni-CDs exhibit significant absorption in the NIR-II region with a distinguished PCE as high as 76.1% (1064 nm) and have excellent photostability and biocompatibility. Furthermore, the Ni-CDs can be employed as photothermal, photoacoustic, and magnetic resonance imaging contrast agents because of their outstanding photothermal effect and instinctive paramagnetic feature. The Ni-CDs demonstrate significant PTT efficacy of tumor upon 1064 nm irradiation with a low power density (0.5 W cm⁻²). The Ni-CDs can be eliminated from the body via a renal filtration pathway, thereby minimizing their long-term biotoxicity. Therefore, this work provides a simple and feasible approach to develop photothermal agents with remarkable PCE in the NIR-II region, presenting good biosafety for multimodal imaging-guided PTT of tumor.     

NIR Mechanoluminescence from Cr3+ Activated Y3Al5O12 with Intense Zero Phonon line

Mechanoluminescence (ML) materials with long-wavelength emission bands are essential for future in vivo bioimaging, non-destructive testing of solids, etc. The lack of a defined mechanism, however, prevents the application of near infrared ML materials above 650 nm in several new fields. Here, the addition of Ga³⁺ ions to Y₃Al₅O₁₂: Cr³⁺ manipulates matrix microstructure evolution, boosting near-infrared (NIR) zero-phonon line (ZPL) stress optical output of the Cr³⁺ ion at 688 nm. The key factor changing the crystal field intensity D_q/B due to the addition of Ga³⁺ ions is what causes the luminescence amplification of ZPL. The ML fabricated by composite polydimethylsiloxane and Y₃Al₄GaO₁₂: Cr³⁺ (YAGG: Cr³⁺) may penetrate chicken feet epidermal tissue and 4 mm pork tissue thanks to the strong NIR ZPL emission of YAGG: Cr³⁺ phosphor. This discovery of enhancing near-infrared ZPL intensity by solid solution provides us with a new technique for optimizing NIR ML materials, as well as a new prospect for NIR ML materials in biological applications.     

天然方钠石的近红外发光特性

采用高温固相法制备了天然方钠石近红外发光材料.测定了荧光粉的X射线衍射(X Ray Diffraction,XRD)谱以及室温下的光致近红外发射光谱和激发光谱.在600nm可见光的激发下,天然方钠石粉末中的Mn5+离子(3A2-1E跃迁)发射了主发射峰位于1200 nm的近红外光谱.在500 nm可见光的激发下,该粉末中的Fe2+离子(3T1-5E)发射了主发射峰位于1000 nm的近红外光谱.这种现象对于提高硅太阳能电池的效率可能具有积极意义.     

Simultaneous Deep Tracking of Stem Cells by Surface Enhanced Raman Imaging Combined with Single-Cell Tracking by NIR-II Imaging in Myocardial Infarction

Stem cell therapy has been used as a potential approach for the treatment of myocardial infarction (MI) over the last two decades. Imaging cellular behaviors of the transplanted stem cells with deep tissue penetration and high precision imaging modalities is crucial for the clinical translation of stem cell therapy approaches for MI. Herein, a gold nanostar (Au-Star) based second near-infrared window (NIR-II) fluorescence/surface enhanced Raman scattering dual-modal imaging probe (gold nanostar-3.3′-diethylthiatricarbocyanine iodide-silver sulfide nanoparticles, Au-Star-DTTC-Ag₂S NPs, GDS NPs) is designed for labeling and precise tracking of the stem cells. The Ag₂S compartment generates strong NIR-II emission, which compensates for the deficiencies of bioluminescent imaging and enables the dynamic observation of in vivo cellular behavior. Subsequently, the specific Raman signal of Au-Star-DTTC compartment enables high-resolution imaging, which could effectively delineate stem cells from the surrounding normal tissues, even at a single-cell resolution. Using this imaging and tracking approach, it is able to track stem cells in hypodermic and MI models, with high resolution and depth-independent imaging capabilities, which have not been reported in any other cell tracking platform. This two-armed imaging toolkit offers new opportunities for a wide range of mechanistic stem cell therapy investigations in different organs.     

Multimode Emission from Lanthanide-Based Metal–Organic Frameworks for Advanced Information Encryption

Although remarkable progress on luminescent materials is made in advanced optical information storage and anti-counterfeiting applications, many challenges still remain in these fields. Currently, most luminescent materials are based on a single photoluminescent model that can be easily imitated by substitutes. In this work, a series of multimodal emission lanthanide-based metal–organic frameworks (MOFs) are developed, where they emit red and green light originating from Eu³⁺ and Tb³⁺ under ultraviolet light irradiation. Meanwhile, under 980 nm near-infrared laser irradiation, these MOFs show cyan upconversion cooperative luminescence derived from Yb³⁺ and characteristic upconversion luminescence from lanthanide activators (Eu³⁺, Tb³⁺, or Ho³⁺), respectively. Based on the integrated optical functionality, the functional information storage applications are successfully designed, which indicates that multimodal emission features can be easily detected under ultraviolet lamps (254 or 393 nm) or 980 nm near-infrared laser. And, the unique optical features show a high level of security in the advanced information storage application, which would be sufficiently complex to be forged.     

Tumor-Activated Photosensitization and Size Transformation of Nanodrugs

Effective intratumoral distribution of anticancer agents with good tumor penetration is of practical importance for photo-chemotherapy. Herein, a metal-organic framework (MOF) assisted strategy is reported for smart delivery of aggregation-induced emission photosensitizer (AIE PS) and chemodrug for deep tumor penetration to realize effective image-guided photo-chemotherapy. A newly designed AIE PS is loaded inside an iron(III) carboxylate-based MOF, MIL-100, to produce PS@MIL-100, which is encapsulated by doxorubicin (Dox) conjugated poly(ethylene glycol) methyl ether (PEG) to yield Dox-PEG-PS@MIL nanoparticles (NPs) with a diameter of 120 nm. After Dox-PEG-PS@MIL NPs reached the tumor site, intratumoral H₂O₂ can cause the release of the loaded PS at the tumor surface for activatable photodynamic therapy (PDT). The Dox-PEG segment is simultaneously triggered to self-assemble into ultrasmall Dox NPs. Under light irradiation, PDT is activated at the tumor surface, synergistically enhancing the tumor penetration of Dox NPs along with their ultrasmall size. After endocytosis of Dox NPs, free Dox is released from Dox NPs under low pH to enter cell nuclei for effective chemotherapy. Accompanied by bright far-red/near-infrared emission from the PS, image-guided photo-chemotherapy with enhanced efficacy is achieved.     

Near-Infrared Mechanoluminescence of Cr3+ Doped Gallate Spinel and Magnetoplumbite Smart Materials

Mechanoluminescence (ML), as an optical response to deformation stimuli, shows great potential in high-end stress sensing, ultrasonic field visualization, and multidimensional anti-counterfeiting. However, processive practical applications in bio-medicine are constrained by the discovery of near-infrared (NIR) ML materials. Unlike lanthanides (Ln³⁺) with sharp multiplets, two kinds of Cr³⁺-doped NIR ML materials, gallate spinel (ZnGa₂O₄:Cr³⁺, Zn₃Ga₂GeO₈:Cr³⁺) and gallate magnetoplumbite (SrGa₁₂O₁₉:Cr³⁺) are here reported. Owing to the intrinsic cation antisite defects and cation vacancies in the matrix, these materials exhibit bright NIR ML under a relatively low load (20 N). In particular for SrGa₁₂O₁₉:Cr³⁺ (750 nm, peak; 100 nm, FWHM) with low persistent luminescence (PersL) interference, the ML behavior can be further rejuvenated under UV and sunlight irradiation. SrGa₁₂O₁₉:Cr³⁺ also shows bright NIR emission under photo- and thermo-stimulation. Owing to their excellent tissue penetration and concealment capability, NIR ML materials show great potential in the fields of bio-medicine and anti-counterfeiting.