A Near‐Infrared Responsive Drug Sequential Release System for Better Eradicating Amyloid Aggregates

Polyphenol compounds, such as curcumin, rutin, rifampicin, can inhibit Aβ aggregation and decrease reactive oxygen species (ROS), and have received much attention in recent years for Alzheimer's disease (AD) treatment. However, the excess metal ions in amyloid plaque can chelate to polyphenol compounds. It significantly declines the efficacy of polyphenol compounds when used in the clinic. In this report, a near‐infrared (NIR)‐caged upconversion responsive system UCNP@SiO₂@Cur/CQ is designed and synthesized to control drug sequential release by regulating NIR laser. When the system is irradiated at low intensity of the NIR laser, the caged metal chelator, clioquinol (CQ), is first released for removing free metal ions, which affects the efficacy of curcumin. Subsequently, the strongly caged curcumin is released with increasing the intensity of NIR light. In this way, the treatment efficacy of curcumin is improved. This NIR‐caged drug release system can not only remove Cu²⁺ but also clean superfluous ROS. Therefore, developing controllable sequential drug releasing may provide clinical benefits of combination treatment of AD. To the best of our knowledge, this work reports for the first time that a sequentially controlled system can overcome the interference of metal ions on polyphenol compounds for AD treatment.     

Near‐Infrared Activated Black Phosphorus as a Nontoxic Photo‐Oxidant for Alzheimer's Amyloid‑β Peptide

The inhibition of amyloid‐β (Aβ) aggregation by photo‐oxygenation has become an effective way of treating Alzheimer's disease (AD). New near‐infrared (NIR) activated treatment agents, which not only possess high photo‐oxygenation efficiency, but also show low biotoxicity, are urgently needed. Herein, for the first time, it is demonstrated that NIR activated black phosphorus (BP) could serve as an effective nontoxic photo‐oxidant for amyloid?β peptide in vitro and in vivo. The nanoplatform BP@BTA (BTA: one of thioflavin‐T derivatives) possesses high affinity to the Aβ peptide due to specific amyloid selectivity of BTA. Importantly, under NIR light, BP@BTA can significantly generate a high quantum yield of singlet oxygen (¹O₂) to oxygenate Aβ, thereby resulting in inhibiting the aggregation and attenuating Aβ‐induced cytotoxicity. In addition, BP could finally degrade into nontoxic phosphate, which guarantees the biosafety. Using transgenic Caenorhabditis elegans CL2006 as AD model, the results demonstrate that the ¹O₂‐generation system could dramatically promote life‐span extension of CL2006 strain by decreasing the neurotoxicity of Aβ.     

Dual‐Modal NIR‐Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid‐β Species In Vivo

Senile plaques, the extracellular deposit of amyloid‐β (Aβ) peptides, are one of the neuropathological hallmarks found in Alzheimer's disease (AD) brain. The current method of brain imaging of amyloid plaques based on positron emission tomography (PET) is expensive and invasive with low spatial resolution. Thus, the development of sensitive and nonradiative amyloid‐β (Aβ)‐specific contrast agents is highly important and beneficial to achieve early AD detection, monitor the disease progression, and evaluate the effectiveness of potential AD drugs. Here a neuroprotective dual‐modal nanoprobe developed by integrating highly Aβ‐specific and turn‐on fluorescence cyanine sensors with superparamagnetic iron oxide nanoparticles as an effective near‐infrared imaging (NIRI)/magnetic resonance imaging (MRI) contrast agent for imaging of Aβ species in vivo is reported. This Aβ‐specific probe is found not only nontoxic and noninvasive, but also highly blood brain barrier permeable. It also shows a potent neuroprotective effect against Aβ‐induced toxicities. This nanoprobe is successfully applied for in vivo fluorescence imaging with high sensitivity and selectivity to Aβ species, and MRI with high spatial resolution in an APP/PS1 transgenic mice model. Its potential as a powerful in vivo dual‐modal imaging tool for early detection and diagnosis of AD in humans is affirmed.     

Near‐Infrared Upconversion Mesoporous Cerium Oxide Hollow Biophotocatalyst for Concurrent pH‐/H2O2‐Responsive O2‐Evolving Synergetic Cancer Therapy

Tumor hypoxia is typically presented in the central region of solid tumors, which is mainly caused by an inadequate blood flow and oxygen supply. In the conventional treatment of hypoxic human tumors, not only the oxygen‐dependent photodynamic therapy (PDT), but also antitumor drug‐based chemotherapy, is considerably limited. The use of direct oxygen delivering approach with oxygen‐dependent PDT or chemotherapy may potentiate the reactive oxygen species (ROS)‐mediated cytotoxicity of the drug toward normal tissues. Herein, a synergetic one‐for‐all mesoporous cerium oxide upconversion biophotocatalyst is developed to achieve intratumorally endogenous H₂O₂‐responsive self‐sufficiency of O₂ and near‐infrared light controlled PDT simultaneously for overcoming hypoxia cancer. Furthermore, the sufficient O₂ plays an important role in overcoming the chemotherapeutic drug‐resistant cancer caused by hypoxia, therefore inducing tumor cell apoptosis significantly.     

Integration of IR‐808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR‐excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR‐808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)‐functionalized silica layer is developed for PDT agent. The two booster effectors (dye‐sensitization and core–shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS₂ nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS₂ nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.     

Amyloid‐β Aggregation with Gold Nanoparticles on Brain Lipid Bilayer

Understanding and manipulating amyloid‐β (Aβ) aggregation provide key knowledge and means for the diagnosis and cure of Alzheimer's disease (AD) and the applications of Aβ‐based aggregation systems. Here, we studied the formation of various Aβ aggregate structures with gold nanoparticles (AuNPs) and brain total lipid extract‐based supported lipid bilayer (brain SLB). The roles of AuNPs and brain SLB in forming Aβ aggregates were studied in real time, and the structural details of Aβ aggregates were monitored and analyzed with the dark‐field imaging of plasmonic AuNPs that allows for long‐term in situ imaging of Aβ aggregates with great structural details without further labeling. It was shown that the fluid brain SLB platform provides the binding sites for Aβ and drives the fast and efficient formation of Aβ aggregate structures and, importantly, large Aβ plaque structures (>15 μm in diameter), a hallmark for AD, were formed without going through fibril structures when Aβ peptides were co‐incubated with AuNPs on the brain SLB. The dark‐field scattering and circular dichroism‐correlation data suggest that AuNPs were heavily involved with Aβ aggregation on the brain SLB and less α‐helix, less β‐sheet and more random coil structures were found in large plaque‐like Aβ aggregates.     

Albumin Nanoshell Encapsulation of Near‐Infrared‐Excitable Rare‐Earth Nanoparticles Enhances Biocompatibility and Enables Targeted Cell Imaging

The use of traditional fluorophores for in vivo imaging applications is limited by poor quantum yield, poor tissue penetration of the excitation light, and excessive tissue autofluorescence, while the use of inorganic fluorescent particles that offer a high quantum yield is frequently limited due to particle toxicity. Rare‐earth‐doped nanoparticles that utilize near‐infrared upconversion overcome the optical limitations of traditional fluorophores, but are not typically suitable for biological application due to their insolubility in aqueous solution, lack of functional surface groups for conjugation of biomolecules, and potential cytotoxicity. A new approach to establish highly biocompatible and biologically targetable nanoshell complexes of luminescent rare‐earth‐doped NaYF₄ nanoparticles (REs) excitable with 920–980 nm near‐infrared light for biomedical imaging applications is reported. The approach involves the encapsulation of NaYF₄ nanoparticles doped with Yb and Er within human serum albumin nanoshells to create water‐dispersible, biologically functionalizable composite particles. These particles exhibit narrow size distributions around 200 nm and are stable in aqueous solution for over 4 weeks. The albumin shell confers cytoprotection and significantly enhances the biocompatibility of REs even at concentrations above 200 µg REs mL^?1. Composite particles conjugated with cyclic arginine‐glycine‐aspartic acid (cRGD) specifically target both human glioblastoma cell lines and melanoma cells expressing α_vβ₃ integrin receptors. These findings highlight the promise of albumin‐encapsulated rare‐earth nanoparticles for imaging cancer cells in vitro and the potential for targeted imaging of disease sites in vivo.     

A Modular System for the Design of Stimuli‐Responsive Multifunctional Nanoparticle Aggregates by Use of Host–Guest Chemistry

A self‐assembly approach for the design of multifunctional nanomaterials consisting of different nanoparticles (gold, iron oxide, and lanthanide‐doped LiYF₄) is developed. This modular system takes advantage of the light‐responsive supramolecular host–guest chemistry of β‐cyclodextrin and arylazopyrazole, which enables the dynamic and reversible self‐assembly of particles to spherical nanoparticle aggregates in aqueous solution. Due to the magnetic iron oxide nanoparticles, the aggregates can be manipulated by an external magnetic field leading to the formation of linear structures. As a result of the integration of upconversion nanoparticles, the aggregates are additionally responsive to near‐infrared light and can be redispersed by use of the upconversion effect. By varying the nanoparticle and linker concentrations the composition, size, shape, and properties of the multifunctional nanoparticle aggregates can be fine‐tuned.     

Multifunctional Yolk‐in‐Shell Nanoparticles for pH‐triggered Drug Release and Imaging

Multifunctional nanoparticles are synthesized for both pH‐triggered drug release and imaging with radioluminescence, upconversion luminescent, and magnetic resonance imaging (MRI). The particles have a yolk‐in‐shell morphology, with a radioluminescent core, an upconverting shell, and a hollow region between the core and shell for loading drugs. They are synthesized by controlled encapsulation of a radioluminescent nanophosphor yolk in a silica shell, partial etching of the yolk in acid, and encapsulation of the silica with an upconverting luminescent shell. Metroxantrone, a chemotherapy drug, was loaded into the hollow space between X‐ray phosphor yolk and up‐conversion phosphor shell through pores in the shell. To encapsulate the drug and control the release rate, the nanoparticles are coated with pH‐responsive biocompatible polyelectrolyte layers of charged hyaluronic acid sodium salt and chitosan. The nanophosphors display bright luminescence under X‐ray, blue light (480 nm), and near infrared light (980 nm). They also served as T₁ and T₂ MRI contrast agents with relaxivities of 3.5 mM^?1 s^?1 (r₁) and 64 mM^?1s^?1 (r₂). These multifunctional nanocapsules have applications in controlled drug delivery and multimodal imaging.     

2D Perovskites with Giant Excitonic Optical Nonlinearities for High‐Performance Sub‐Bandgap Photodetection

Two‐dimensional (2D) perovskites have proved to be promising semiconductors for photovoltaics, photonics, and optoelectronics. Here, a strategy is presented toward the realization of highly efficient, sub‐bandgap photodetection by employing excitonic effects in 2D Ruddlesden–Popper‐type halide perovskites (RPPs). On near resonance with 2D excitons, layered RPPs exhibit degenerate two‐photon absorption (D‐2PA) coefficients as giant as 0.2–0.64 cm MW^?1. 2D RPP‐based sub‐bandgap photodetectors show excellent detection performance in the near‐infrared (NIR): a two‐photon‐generated current responsivity up to 1.2 × 10⁴ cm² W^?2 s^?1, two orders of magnitude greater than InAsSbP‐pin photodiodes; and a dark current as low as 2 pA at room temperature. More intriguingly, layered‐RPP detectors are highly sensitive to the light polarization of incoming photons, showing a considerable anisotropy in their D‐2PA coefficients (β_[001]/β_[011] = 2.4, 70% larger than the ratios reported for zinc‐blende semiconductors). By controlling the thickness of the inorganic quantum well, it is found that layered RPPs of (C₄H₉NH₃)₂(CH₃NH₃)Pb₂I₇ can be utilized for three‐photon photodetection in the NIR region.     

From UV to Near‐Infrared Light‐Responsive Metal–Organic Framework Composites: Plasmon and Upconversion Enhanced Photocatalysis

The exploitation of photocatalysts that harvest solar spectrum as broad as possible remains a high‐priority target yet grand challenge. In this work, for the first time, metal–organic framework (MOF) composites are rationally fabricated to achieve broadband spectral response from UV to near‐infrared (NIR) region. In the core–shell structured upconversion nanoparticles (UCNPs)‐Pt@MOF/Au composites, the MOF is responsive to UV and a bit visible light, the plasmonic Au nanoparticles (NPs) accept visible light, whereas the UCNPs absorb NIR light to emit UV and visible light that are harvested by the MOF and Au once again. Moreover, the MOF not only facilitates the generation of “bare and clean” Au NPs on its surface and realizes the spatial separation for the Au and Pt NPs, but also provides necessary access for catalytic substrates/products to Pt active sites. As a result, the optimized composite exhibits excellent photocatalytic hydrogen production activity (280 µmol g^?1 h^?1) under simulated solar light, and the involved mechanism of photocatalytic H₂ production under UV, visible, and NIR irradiation is elucidated. Reportedly, this is an extremely rare study on photocatalytic H₂ production by light harvesting in all UV, visible, and NIR regions.     

Glutathione Depletion in a Benign Manner by MoS2‐Based Nanoflowers for Enhanced Hypoxia‐Irrelevant Free‐Radical‐Based Cancer Therapy

Tumor hypoxia significantly diminishes the efficacy of reactive oxygen species (ROS)‐based therapy, mainly because the generation of ROS is highly oxygen dependent. Recently reported hypoxia‐irrelevant radical initiators (AIBIs) exhibit promising potential for cancer therapy under different oxygen tensions. However, overexpressed glutathione (GSH) in cancer cells would potently scavenge the free radicals produced from AIBI before their arrival to the specific site and dramatically limit the therapeutic efficacy. A synergistic antitumor platform (MoS₂@AIBI‐PCM nanoflowers) is constructed by incorporating polyethylene‐glycol‐functionalized molybdenum disulfide (PEG‐MoS₂) nanoflowers with azo initiator and phase‐change material (PCM). Under near‐infrared laser (NIR) irradiation, the photothermal feature of PEG‐MoS₂ induces the decomposition of AIBI to produce free radicals. Furthermore, PEG‐MoS₂ can facilitate GSH oxidation without releasing toxic metal ions, greatly promoting tumor apoptosis and avoiding the introduction of toxic metal ions. This is the first example of the use of intelligent MoS₂‐based nanoflowers as a benign GSH scavenger for enhanced cancer treatment.     

Energy Upconversion in GaP/GaNP Core/Shell Nanowires for Enhanced Near‐Infrared Light Harvesting

Semiconductor nanowires (NWs) have recently gained increasing interest due to their great potential for photovoltaics. A novel material system based on GaNP NWs is considered to be highly suitable for applications in efficient multi‐junction and intermediate band solar cells. This work shows that though the bandgap energies of GaN_xP_1‐x alloys lie within the visible spectral range (i.e., within 540–650 nm for the currently achievable x < 3%), coaxial GaNP NWs grown on Si substrates can also harvest infrared light utilizing energy upconversion. This energy upconversion can be monitored via anti‐Stokes near‐band‐edge photoluminescence (PL) from GaNP, visible even from a single NW. The dominant process responsible for this effect is identified as being due to two‐step two‐photon absorption (TS‐TPA) via a deep level lying at about 1.28 eV above the valence band, based on the measured dependences of the anti‐Stokes PL on excitation power and wavelength. The formation of the defect participating in the TS‐TPA process is concluded to be promoted by nitrogen incorporation. The revealed defect‐mediated TS‐TPA process can boost efficiency of harvesting solar energy in GaNP NWs, beneficial for applications of this novel material system in third‐generation photovoltaic devices.     

Polyhydroxylated Metallofullerenols Stimulate IL‐1β Secretion of Macrophage through TLRs/MyD88/NF‐κB Pathway and NLRP3 Inflammasome Activation

Polyhydroxylated fullerenols especially gadolinium endohedral metallofullerenols (Gd@C₈₂(OH)₂₂) are shown as a promising agent for antitumor chemotherapeutics and good immunoregulatory effects with low toxicity. However, their underlying mechanism remains largely unclear. We found for the first time the persistent uptake and subcellular distribution of metallofullerenols in macrophages by taking advantages of synchrotron‐based scanning transmission X‐ray microscopy (STXM) with high spatial resolution of 30 nm. Gd@C₈₂(OH)₂₂ can significantly activate primary mouse macrophages to produce pro‐inflammatory cytokines like IL‐1β. Small interfering RNA (siRNA) knockdown shows that NLRP3 in?ammasomes, but not NLRC4, participate in fullerenol‐induced IL‐1β production. Potassium efflux, activation of P2X₇ receptor and intracellular reactive oxygen speciesare also important factors required for fullerenols‐induced IL‐1β release. Stronger NF‐κB signal triggered by Gd@C₈₂(OH)₂₂ is in agreement with higher pro‐IL‐1β expression than C₆₀(OH)₂₂. Interestingly, TLR4/MyD88 pathway but not TLR2 mediates IL‐1β secretion in Gd@C₈₂(OH)₂₂ exposure confirmed by macrophages from MyD88^?/?/TLR4^?/?/TLR2^?/? knockout mice, which is different from C₆₀(OH)₂₂. Our work demonstrated that fullerenols can greatly activate macrophage and promote IL‐1β production via both TLRs/MyD88/NF‐κB pathway and NLRP3 inflammasome activation, while Gd@C₈₂(OH)₂₂ had stronger ability C₆₀(OH)₂₂ due to the different electron affinity on the surface of carbon cage induced by the encaged gadolinium ion.     

Detection of β‐Amyloid by Sialic Acid Coated Bovine Serum Albumin Magnetic Nanoparticles in a Mouse Model of Alzheimer's Disease

The accumulation and formation of β‐amyloid (Aβ) plaques in the brain are distinctive pathological hallmarks of Alzheimer's disease (AD). Designing nanoparticle (NP) contrast agents capable of binding with Aβ highly selectively can potentially facilitate early detection of AD. However, a significant obstacle is the blood brain barrier (BBB), which can preclude the entrance of NPs into the brain for Aβ binding. In this work, bovine serum albumin (BSA) coated NPs are decorated with sialic acid (NP‐BSA_x‐Sia) to overcome the challenges in Aβ imaging in vivo. The NP‐BSA_x‐Sia is biocompatible with high magnetic relaxivities, suggesting that they are suitable contrast agents for magnetic resonance imaging (MRI). The NP‐BSA_x‐Sia binds with Aβ in a sialic acid dependent manner with high selectivities toward Aβ deposited on brains and cross the BBB in an in vitro model. The abilities of these NPs to detect Aβ in vivo in human AD transgenic mice by MRI are evaluated without the need to coinject mannitol to increase BBB permeability. T₂*‐weighted MRI shows that Aβ plaques in mouse brains can be detected as aided by NP‐BSA_x‐Sia, which is confirmed by histological analysis. Thus, NP‐BSA_x‐Sia is a promising new tool for noninvasive in vivo detection of Aβ plaques.     

A Highly Efficient and Photostable Photosensitizer with Near‐Infrared Aggregation‐Induced Emission for Image‐Guided Photodynamic Anticancer Therapy

Photodynamic therapy (PDT), which relies on photosensitizers (PS) and light to generate reactive oxygen species to kill cancer cells or bacteria, has attracted much attention in recent years. PSs with both bright emission and efficient singlet oxygen generation have also been used for image‐guided PDT. However, simultaneously achieving effective ¹O₂ generation, long wavelength absorption, and stable near‐infrared (NIR) emission with low dark toxicity in a single PS remains challenging. In addition, it is well known that when traditional PSs are made into nanoparticles, they encounter quenched fluorescence and reduced ¹O₂ production. In this contribution, these challenging issues have been successfully addressed through designing the first photostable photosensitizer with aggregation‐induced NIR emission and very effective ¹O₂ generation in aggregate state. The yielded nanoparticles show very effective ¹O₂ generation, bright NIR fluorescence centered at 820 nm, excellent photostability, good biocompatibility, and negligible dark in vivo toxicity. Both in vitro and in vivo experiments prove that the nanoparticles are excellent candidates for image‐guided photodynamic anticancer therapy.     

Integration of Multiple Plasmonic and Co‐Catalyst Nanostructures on TiO2 Nanosheets for Visible‐Near‐Infrared Photocatalytic Hydrogen Evolution

Utilization of visible and near‐infrared light has always been the pursuit of photocatalysis research. In this article, an approach is developed to integrate dual plasmonic nanostructures with TiO₂ semiconductor nanosheets for photocatalytic hydrogen production in visible and near‐infrared spectral regions. Specifically, the Au nanocubes and nanocages used in this work can harvest visible and near‐infrared light, respectively, and generate and inject hot electrons into TiO₂. Meanwhile, Pd nanocubes that can trap the energetic electrons from TiO₂ and efficiently participate in the hydrogen evolution reaction are employed as co‐catalysts for improved catalytic activity. Enabled by this unique integration design, the hydrogen production rate achieved is dramatically higher than those of its counterpart structures. This work represents a step toward the rational design of semiconductor–metal hybrid structures for broad‐spectrum photocatalysis.     

Iridium(III) Complex–Derived Polymeric Micelles with Low Dark Toxicity and Strong NIR Excitation for Phototherapy and Chemotherapy

Iridium(III) complexes are potent candidates for photodynamic therapy. However, their clinical usage is impeded by their poor water solubility, high dark toxicity, and negligible absorption in near‐infrared region (NIR region). Here, it is proposed to solve these challenges by developing an iridium(III) complexe‐based polymeric micelle system. This system is self‐assembled using an iridium(III) complex‐containing amphiphilic block polymer. The upconversion nanoparticles are included in the polymeric micelles to permit NIR excitation. Compared with the nonformulated iridium(III) complexes, under NIR stimulation, this polymeric micelle system exhibits higher ¹O₂ generation efficiency, negligible dark toxicity, excellent tumor‐targeting ability, and synergistic phototherapy–chemotherapy effect both in vitro and in vivo.     

Spatially Confined Growth of Fullerene to Super‐Long Crystalline Fibers in Supramolecular Gels for High‐Performance Photodetector

As a superstar organic semiconductor, fullerene (C₆₀) is versatile in nature for its multiple photoelectric applications. However, owing to its natural 0D structure, a challenge still remains unbeaten as to growth of 1D fullerene crystals with tunable sizes. Herein, reported is an efficient approach to grow C₆₀ as super‐long crystalline fibers with tunable lengths and diameters in supramolecular gel by synergic changes of anti‐solvent, gel length, crystallization time or fullerene concentration. As a result, the crystalline C₆₀ fibers can be modulated to as long as 70 mm and 70 000 in their length‐to‐width ratio. In this case, the gel 3D network provides spatial confinements for the growth of 1D crystal along the directional dispersion of anti‐solvent. The fabricated fullerene device exhibits high responsivity (2595.6 mA W^‐1) and high specific detectivity (2.7 × 10¹² Jones) at 10 V bias upon irradiation of 400 nm incident light. The on/off ratio and its quantum efficiency are near to 540 and about 800%, respectively, and importantly, its photoelectric property remains very stable after storage in air for six months. Therefore, spatially confined growth of fullerene in supramolecular gels will be another crucial strategy to synthesize 1D semiconductor crystals for photoelectrical device applications in near future.     

Chromophore‐Modified Highly Selective Ratiometric Upconversion Nanoprobes for Detection of ONOO−‐Related Hepatotoxicity In Vivo

Acute hepatitis is a major problem affecting public health and has attracted more and more attention. Generally, as the standard means, blood tests are taken for evaluating hepatitis. However, such tests fail to accurately reflect the level of hepatitis in vivo. Herein, two highly selective ratiometric fluorescent probes are designed to track peroxynitrite (ONOO^?) as the hepatitis indicator, and further evaluate acute liver injury in vivo through dye‐grafted upconversion nanoparticles (UCNPs). Specifically, upconversion luminescence of nanoprobes at 540 or 660 nm can be quenched by the designed and synthesized chromophore E‐CC or H‐CC, that can be destroyed by ONOO^? via energy transfer (ET) process, while the upconversion luminescence intensity at 810 nm remains the same. Thus, the developed nanoprobes can be used for ratiometric detection (I₅₄₀/I₆₆₀ or I₆₆₀/I₈₁₀) of ONOO^?. Moreover, the developed near infrared ratiometric nanoprobes can highly selectively detect ONOO^?, which can eliminate the interference of HOCl and SO₃^2?. Finally, it is demonstrated that this highly selective ratiometric nanosystem can achieve effective detection of ONOO^? in living cells and CCl₄‐induced acute liver injury models. It provides some reference value for clinical detection of hepatotoxicity.