Design and synthesis of a small molecular NIR-II chemiluminescence probe for in vivo-activated H2S imaging.

Chemiluminescence (CL) with the elimination of excitation light and minimal autofluorescence interference has been wieldy applied in biosensing and bioimaging. However, the traditional emission of CL probes was mainly in the range of 400 to 650 nm, leading to undesired resolution and penetration in a biological object. Therefore, it was urgent to develop CL molecules in the near-infrared window [NIR, including NIR-I (650 to 900 nm) and near-infrared-II (900 to 1,700 nm)], coupled with unique advantages of long-time imaging, sensitive response, and high resolution at depths of millimeters. However, no NIR-II CL unimolecular probe has been reported until now. Herein, we developed an H2S-activated NIR-II CL probe [chemiluminiscence donor 950, (CD-950)] by covalently connecting two Schaap's dioxetane donors with high chemical energy to a NIR-II fluorophore acceptor candidate via intramolecular CL resonance energy transfer strategy, thereby achieving high efficiency of 95%. CD-950 exhibited superior capacity including long-duration imaging (~60 min), deeper tissue penetration (~10 mm), and specific H2S response under physiological conditions. More importantly, CD-950 showed detection capability for metformin-induced hepatotoxicity with 2.5-fold higher signal-to-background ratios than that of NIR-II fluorescence mode. The unimolecular NIR-II CL probe holds great potential for the evaluation of drug-induced side effects by tracking its metabolites in vivo, further facilitating the rational design of novel NIR-II CL-based detection platforms.

X-ray Activated Nanoprodrug for Visualization of Cortical Microvascular Alterations and NIR-II Image-Guided Chemo-Radiotherapy of Glioblastoma.

The permeability of the highly selective blood-brain barrier (BBB) to anticancer drugs and the difficulties in defining deep tumor boundaries often reduce the effectiveness of glioma treatment. Thus, exploring the combination of multiple treatment modalities under the guidance of second-generation near-infrared (NIR-II) window fluorescence (FL) imaging is considered a strategic approach in glioma theranostics. Herein, a hybrid X-ray-activated nanoprodrug was developed to precisely visualize the structural features of glioma microvasculature and delineate the boundary of glioma for synergistic chemo-radiotherapy. The nanoprodrug comprised down-converted nanoparticle (DCNP) coated with X-ray sensitive poly(Se-Se/DOX-co-acrylic acid) and targeted Angiopep-2 peptide (DCNP@P(Se-DOX)@ANG). Because of its ultrasmall size and the presence of DOX, the nanoprodrug could easily cross BBB to precisely monitor and localize glioblastoma via intracranial NIR-II FL imaging and synergistically administer antiglioblastoma chemo-radiotherapy through specific X-ray-induced DOX release and radiosensitization. This study provides a novel and effective strategy for glioblastoma imaging and chemo-radiotherapy.

Molecular radio afterglow probes for cancer radiodynamic theranostics.

X-ray-induced afterglow and radiodynamic therapy tackle the tissue penetration issue of optical imaging and phototherapy. However, inorganic nanophosphors used in this therapy have their radio afterglow dynamic function as always on, limiting the detection specificity and treatment efficacy. Here we report organic luminophores (IDPAs) with near-infrared afterglow and 1O2 production after X-ray irradiation for cancer theranostics. The in vivo radio afterglow of IDPAs is >25.0 times brighter than reported inorganic nanophosphors, whereas the radiodynamic production of 1O2 is >5.7 times higher than commercially available radio sensitizers. The modular structure of IDPAs permits the development of a smart molecular probe that only triggers its radio afterglow dynamic function in the presence of a cancer biomarker. Thus, the probe enables the ultrasensitive detection of a diminutive tumour (0.64 mm) with superb contrast (tumour-to-background ratio of 234) and tumour-specific radiotherapy for brain tumour with molecular precision at low dosage. Our work reveals the molecular guidelines towards organic radio afterglow agents and highlights new opportunities for cancer radio theranostics.

Drug-Free Antimicrobial Nanomotor for Precise Treatment of Multidrug-Resistant Bacterial Infections.

Manufacturing heteronanostructures with specific physicochemical characteristics and tightly controllable designs is very appealing. Herein, we reported NIR-II light-driven dual plasmonic (AuNR-SiO2-Cu7S4) antimicrobial nanomotors with an intended Janus configuration through the overgrowth of copper-rich Cu7S4 nanocrystals at only one high-curvature site of Au nanorods (Au NRs). These nanomotors were applied for photoacoustic imaging (PAI)-guided synergistic photothermal and photocatalytic treatment of bacterial infections. Both the photothermal performance and photocatalytic activity of the nanomotors are dramatically improved owing to the strong plasmon coupling between Au NRs and the Cu7S4 component and enhanced energy transfer. The motion behavior of nanomotors promotes transdermal penetration and enhances the matter-bacteria interaction. More importantly, the directional navigation and synergistic antimicrobial activity of the nanomotors could be synchronously driven by NIR-II light. The marriage of active motion and enhanced antibacterial activity resulted in the expected good antibacterial effects in an abscess infection mouse model.

Ultrasound-Activated NIR Chemiluminescence for Deep Tissue and Tumor Foci Imaging.

Fluorescence imaging requires real-time external light excitation; however, it has the drawbacks of autofluorescence and shallower penetration depth, limiting its application in deep tissue imaging. At the same time, ultrasound (US) has high spatiotemporal resolution, deep penetrability, noninvasiveness, and precise localization of lesions; thus, it can be a promising alternative to light. However, US-activated luminescence has been rarely reported. Herein, an US-activated near-infrared (NIR) chemiluminescence (CL) molecule, namely, PNCL, is designed by protoporphyrin IX as a sonosensitizer moiety and a phenoxy-dioxetane precursor containing a dicyanomethyl chromone acceptor scaffold (NCL) as the US-responsive moiety. After therapeutic US radiation (1 MHz), the singlet oxygen (1O2), as an "intermediary", oxidizes the enol-ether bond of the NCL moiety and then emits NIR light via spontaneous decomposition. Combining the deep penetrability of US with a high signal-to-background ratio of NIR CL, the designed probe PNCL successfully realizes US-activated deep tissue imaging (∼20 mm) and selectively turns on signals in specific tumor foci. Bridging US chemistry with luminescence using an "intermediary" will provide new imaging methods for accurate cancer diagnosis.

A Radio-Pharmaceutical Fluorescent Probe for Synergistic Cancer Radiotherapy and Ratiometric Imaging of Tumor Reactive Oxygen Species.

Radiotherapy (RT) is an effective and widely applied cancer treatment strategy in clinic. However, it usually suffers from radioresistance of tumor cells and severs side effects of excessive radiation dose. Therefore, it is highly significant to improve radiotherapeutic performance and monitor real-time tumor response, achieving precise and safe RT. Herein, an X-ray responsive radio-pharmaceutical molecule containing chemical radiosensitizers of diselenide and nitroimidazole (BBT-IR/Se-MN) is reported. BBT-IR/Se-MN exhibits enhanced radiotherapeutic effect via a multifaceted mechanisms and self-monitoring ROS levels in tumors during RT. Under X-ray irradiation, the diselenide produces high levels of ROS, leading to enhanced DNA damage of cancer cell. Afterwards, the nitroimidazole in the molecule inhibits the damaged DNA repair, offering a synergetic radiosensitization effect of cancer. Moreover, the probe shows low and high NIR-II fluorescence ratios in the absence and presence of ROS, which is suitable for precise and quantitative monitoring of ROS during sensitized RT. The integrated system is successfully applied for radiosensitization and the early prediction of in vitro and in vivo RT efficacy.

Ratiometric Detection of H2S in Liver Injury by Activated Two-Wavelength Photoacoustic Imaging.

Metformin is commonly used for clinical treatment of type-2 diabetes, but long-term or overdose intake of metformin usually causes selective upregulation of H2S level in the liver, resulting in liver injury. Therefore, tracking the changes of H2S content in the liver would contribute to the prevention and diagnosis of liver injury. However, in the literature, there are few reports on ratiometric PA molecular probes for H2S detection in drug-induced liver injury (DILI). Accordingly, here we developed a H2S-activated ratiometric PA probe, namely BDP-H2S, based Aza-BODIPY dye for detecting the H2S upregulation of metformin-induced liver injury. Due to the intramolecular charge transfer (ICT) effect, BDP-H2S exhibited a strong PA signal at 770 nm. Following the response to H2S, its ICT effect was recovered which showed a decrement of PA770 and an enhancement of PA840. The ratiometric PA signal (PA840/PA770) showed excellent H2S selectivity response with a low limit of detection (0.59 µM). Bioimaging experiments demonstrated that the probe has been successfully used for ratiometric PA imaging of H2S in cells and metformin-induced liver injury in mice. Overall, the designed probe emerges as a powerful tool for noninvasive and accurate imaging of H2S level and tracking its distribution and variation in liver in-real time.

In-Situ Assembly of Janus Nanoprobe for Cancer Activated NIR-II Photoacoustic Imaging and Enhanced Photodynamic Therapy.

Inorganic nanoprobes have attracted increasing attention in the biomedical field due to their versatile functionalities and excellent optical properties. However, conventional nanoprobes have a relatively low retention time in the tumor and are mostly applied in the first near-infrared window (NIR-I, 650-950 nm), limiting their applications in accurate and deep tissue imaging. Herein, we develop a Janus nanoprobe, which can undergo tumor microenvironment (TME)-induced aggregation, hence, promoting tumor retention time and providing photoacoustic (PA) imaging in the second NIR (NIR-II, 950-1700 nm) window, and enhancing photodynamic therapy (PDT) effect. Ternary Janus nanoprobe is composed of gold nanorod (AuNR) coated with manganese dioxide (MnO2) and photosensitizer pyropheophorbide-a (Ppa) on two ends of AuNR, respectively, named as MnO2-AuNR-Ppa. In the tumor, MnO2 could be etched by glutathione (GSH) to release Mn2+, which is coordinated with multiple Ppa molecules to induce in situ aggregation of AuNRs. The aggregation of AuNR effectively improves the NIR-II photoacoustic signal in vivo. Moreover, the increased retention time of nanoprobes and GSH reduction in the tumor greatly improve the PDT effect. We believe that this work will inspire further research on specific in situ aggregation of inorganic nanoparticles.

Neodymium (3+)-Coordinated Black Phosphorus Quantum Dots with Retrievable NIR/X-Ray Optoelectronic Switching Effect for Anti-Glioblastoma.

Heteroatom interaction of atomically thin nanomaterials enables the improvement of electronic transfer, band structure, and optical properties. Black phosphorus quantum dots (BP QDs) are considered to be candidate diagnostic and/or therapeutic agents due to their innate biocompatibility and exceptional photochemical effects. However, BP QDs are not competitive regarding second near-infrared (NIR-II) window medical diagnosis and X-ray induced phototherapy. Here, an Nd3+ ion coordinated BP QD (BPNd) is synthesized with the aim to sufficiently improve its performances in NIR-II fluorescence imaging and X-ray induced photodynamic therapy, benefitting from the retrievable NIR/X-ray optoelectronic switching effects between BP QD and Nd3+ ion. Given its ultrasmall size and efficient cargo loading capacity, BPNd can easily cross the blood-brain barrier to precisely monitor the growth of glioblastoma through intracranial NIR-II fluorescence imaging and impede its progression by specific X-ray induced, synergistic photodynamic chemotherapy.

NIR-II Ratiometric Chemiluminescent/Fluorescent Reporters for Real-Time Monitoring and Evaluating Cancer Photodynamic Therapy Efficacy.

The development of probes for early monitoring tumor therapy response may greatly benefit the promotion of photodynamic therapy (PDT) efficacy. Singlet oxygen (1 O2 ) generation is a typical indicator for evaluating PDT efficacy in cancer. However, most existing probes cannot quantitatively detect 1 O2 in vivo due to the high reactivity and transient state, and thus have a poor correlation with PDT response. Herein, a 1 O2 -responsive theranostic platform comprising thiophene-based small molecule (2SeFT-PEG) and photosensitizer Chlorin e6 (Ce6) micelles for real-time monitoring PDT efficacy is developed. After laser irradiation, the Ce6-produced 1 O2 could simultaneously kill cancer and trigger 2SeFT-PEG to produce increased chemiluminescence (CL) and decreased fluorescence (FL) signals variation at 1050 nm in the second near-infrared (NIR-II, 950-1700 nm) window. Significantly, the ratiometric NIR-II CL/FL imaging at 1050 nm could effectively quantify and monitor the concentration of 1 O2 and O2 consumption or recovery, so as to evaluate the therapeutic efficacy of PDT in vivo. Hence, this 1 O2 activated NIR-II CL/FL probe provides an efficient ratiometric optical imaging platform for real-time evaluating PDT effect and precisely guiding the PDT process in vivo.

Plasmonic-Fluorescent Janus Ag/Ag2S Nanoparticles for In Situ H2O2-Activated NIR-II Fluorescence Imaging.

Silver sulfide (Ag2S) has gained widespread attention in second near-infrared (950-1700 nm, NIR-II) window imaging because of its high fluorescence quantum yield and low toxicity. However, its "always on" fluorescence shows inapplicability for targeted molecule-activated biomedical applications. Herein, we first developed a novel silver/silver sulfide Janus nanoparticle (Ag/Ag2S JNP) for specific activatable fluorescence imaging in the NIR-II window. Inner-particle electron compensation from Ag to Ag2S upon laser irradiation endowed JNPs an "off" state of fluorescence, whereas the oxidization of Ag incubated with H2O2, decreasing the electron-transfer effect and illuminating the NIR-II fluorescence of the Ag2S part. In contrast, the absorption of Ag/Ag2S JNPs slightly decreased in an H2O2-dependent manner, showing an activated photoacoustic imaging mechanism. The Ag/Ag2S JNPs were used for noninvasive location and diagnosis of diseases in vivo, such as for liver injury and cancer, with high sensitivity and accuracy.

An Activatable Hybrid Organic-Inorganic Nanocomposite as Early Evaluation System of Therapy Effect.

Delays in evaluating cancer response to radiotherapy (RT) usually reduce therapy effect or miss the right time for treatment optimization. Hence, exploring timely and accurate methods enabling one to gain insights of RT response are highly desirable. In this study, we have developed an apoptosis enzyme (caspase-3) activated nanoprobe for early evaluation of RT efficacy. The nanoprobe bridged the nanogapped gold nanoparticles (AuNNPs) and the second near-infrared window (NIR-II) fluorescent (FL) molecules (IR-1048) through a caspase-3 specific peptide sequence (DEVD) (AuNNP@DEVD-IR1048). After X-ray irradiation, caspase-3 was activated to cut DEVD, turning on both NIR-II FL and PA imaging signals. The increased NIR-II FL/PA signals exhibited a positive correlation with the content of caspase-3. Moreover, the amount of the activated caspase-3 was negatively correlated with the tumor size. The results underscore the role of the caspase-3 activated by X-ray irradiation in bridging the imaging signals variation and tumor inhibition rate. Overall, activatable NIR-II FL/PA imaging was successfully used to timely predict and evaluate the RT efficacy. The evaluation system based on biomarker-triggered living imaging has the capacity to guide treatment decisions for numerous cancer types.

A NO-Responsive Ratiometric Fluorescent Nanoprobe for Monitoring Drug-Induced Liver Injury in the Second Near-Infrared Window.

Currently, drug-induced liver injury (DILI) has become a huge concern for the majority of modern medicine, whereas the diagnosis of DILI is still in its infancy due to the lack of appropriate methods. Herein, based on the fact that nitric oxide (NO) has been recognized as an early unifying, direct, and vital biomarker for DILI, we rationally designed and developed a NO-responsive ratiometric fluorescent nanoprobe DCNP@MPS@IR NO to quantitatively detect NO and monitor DILI in the second near-infrared (NIR-II) window. In the presence of NO, due to the conversion of IR NO into IR RA and excellent stability of the downconversion nanoparticle (DCNP), DCNP@MPS@IR NO could present a "Turn-On" fluorescence signal at 1050 nm under 808 nm excitation (F1050 Em, 808 Ex) and an "Always-On" fluorescence signal at 1550 nm under 980 nm excitation (F1550 Em, 980 Ex), which led to a "Turn-On" ratiometric fluorescence signal F1050 Em, 808 Ex/F1550 Em, 980 Ex. DCNP@MPS@IR NO was then successfully applied in vitro to selectively detect NO, at a linear concentration range of 0-100 µM with a limit of detection of 0.61 µM. In vivo results revealed that DCNP@MPS@IR was available to quantify NO in acetaminophen (APAP)-induced liver injury, monitor DILI, and screen an antidote for APAP through NIR-II ratiometric fluorescence imaging. We envision that our nanoprobe DCNP@MPS@IR NO might become a really useful biotechnology tool for visualizing and early diagnosis of drug-induced liver injury and revealing the mechanism of drug hepatotoxicity in the clinic in the near future.

NIR-II Fluorescent Biodegradable Nanoprobes for Precise Acute Kidney/Liver Injury Imaging and Therapy.

NIR-II fluorescent nanoprobes based on inorganic materials, including rare-earth-doped nanoparticles, single-walled carbon nanotubes, CdS quantum dots (QDs), gold nanoclusters, etc., have gained growing interest in bioimaging applications. However, these nanoprobes are usually not biodegradable and lack therapeutic functions. Herein, we developed novel NIR-II fluorescence (FL) imaging and therapeutic nanoprobes based on black phosphorus QDs (BPQDs), which exhibited excellent biodegradability and high tunability of size-dependent optical properties. By adjusting the size of nanoparticles, BPQDs can specifically accumulate in the kidney or liver. Importantly, a low dosage of BPQDs can effectively protect tissues from reactive oxygen species (ROS)-mediated damage in acute kidney and liver injury, which was real-time monitored by responsive NIR-II fluorescence imaging. Overall, we developed novel NIR-II emitting and therapeutic BPQDs with excellent biodegradability vivo, providing a promising candidate for NIR-II FL imaging and ROS scavenging.

In Situ Activatable Ratiometric NIR-II Fluorescence Nanoprobe for Quantitative Detection of H2S in Colon Cancer.

As key characteristic molecules, several H2S-activated probes have been explored for colon cancer studies. However, a few ratiometric fluorescence (FL) probes with NIR-II emissions have been reported for the quantitative detection of H2S in colon cancer in vivo. Here, we developed an in situ H2S-activatable ratiometric nanoprobe with two NIR-II emission signals for the detection of H2S and intelligently lighting up colon cancer. The nanoprobe comprised a down conversion nanoparticle (DCNP), which emitted NIR-II FL at 1550 nm on irradiation with a 980 nm laser (F1550Em, 980Ex). Further, human serum albumin (HSA) was combined with Ag+ on the surface of DCNP to form a DCNP@HSA-Ag+ nanoprobe. In the presence of H2S, Ag2S quantum dots (QDs) were formed in coated HSA, which emitted FL at approximately 1050 nm on irradiation with an 808 nm laser (F1050Em, 808Ex) through an H2S-induced chemical reaction between H2S and Ag+; however, the FL signal of DCNP was stable at 1550 nm (F1550Em, 980Ex), generating a H2S concentration-dependent ratiometric F1050Em, 808Ex/F1550Em, 980Ex signal. The NIR-II ratiometric nanoprobe was successfully used for the accurate quantitative detection of H2S and the detection of the precise location of colon cancer through an endogenous H2S-induced in situ reduction reaction to form Ag2S QDs. Thus, these findings provide a new strategy for the specific detection of targeted molecules and diagnosis of disease based on the in situ-activatable NIR-II ratiometric FL nanoprobe.

NIR-II Photoacoustic Reporter for Biopsy-Free and Real-Time Assessment of Wilson's Disease.

Wilson's disease (WD) is a rare inherited disorder of copper metabolism with pathological copper hyperaccumulation in some vital organs. However, the clinical diagnosis technique of WD is complicated, aggressive, and time-consuming. In this work, a novel ratiometric photoacoustic (PA) imaging nanoprobe in the NIR-II window is developed to achieve noninvasive, rapid, and accurate Cu2+ quantitative detection in vitro and in vivo. The nanoprobe consists of Cu2+ -responsive IR970 dye and a nonresponsive palladium-coated gold nanorod (AuNR-Pd), achieving a concentration-dependent ratiometric PA970 /PA1260 signal change. The urinary Cu2+ content is detectable within minutes down to a detection limit of 76 × 10-9 m. This report acquisition time is several orders of magnitude shorter than those of existing detection approaches requiring complex procedure. Moreover, utilizing the ratiometric PA nanoprobe, PA imaging enables biopsy-free measurement of the liver Cu2+ content and visualization of the liver Cu2+ biodistribution of WD patient, which avoid the body injury during the clinical Cu2+ test using liver biopsy method. The NIR-II ratiometric PA detection method is simple and noninvasive with super precision, celerity, and simplification, which holds great promise as an alternative to liver biopsy for clinical diagnosis of WD.

NIR-II emissive AIEgen photosensitizers enable ultrasensitive imaging-guided surgery and phototherapy to fully inhibit orthotopic hepatic tumors.

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.

Asymmetric Core-Shell Gold Nanoparticles and Controllable Assemblies for SERS Ratiometric Detection of MicroRNA.

Janus nanogap gold nanoparticles (JAuNNPs) with varying proportions of Au shell coverage of (ca. 100/75/50/25 %) are presented. The internal nanogap between the partial Au shell and core caused asymmetric optical behavior; tunability depends on the degree of Au shell coverage and structural asymmetry. The shell-to-shell or core-to-core JAuNNDs(50 %) were self-assembled from amphiphilic JAuNNPs(50 %) by tuning the hydrophilic and hydrophobic polymer brushes on the Au core or shell. The positions of electromagnetic field enhancement of JAuNNDs varied with geometrical configurations because of hybridized plasmonic coupling effects. Furthermore, DNA linkers were utilized to form JAuNND12 (50 %). By combining with Raman molecules, ratiometric SERS signals could be generated, enabling JAuNND12 (50 %) to image the distribution of miR-21 in living cells and tumors. Asymmetric JAuNNPs allowed facile conjugation of various linkage molecules to fabricate dimeric nanostructures.

In Vivo X-ray Triggered Catalysis of H2 Generation for Cancer Synergistic Gas Radiotherapy.

To date, hydrogen (H2 ) therapy has received widespread attention. However, X-ray triggered sustainable H2 -producing materials with controlled release for cancer treatment have not been reported. Herein, an X-ray triggered sustainable in situ H2 producing platform, Au NR-TiO2 @ZnS:Cu,Co-A(Au-TiO2 @ZnS), composed of Au-amorphous TiO2 nano-dumbbell-shaped heterostructure coated with long afterglow particles, was developed for cancer synergistic H2 -radiotherapy. The mechanism of H2 production was verified by theoretical calculations and in vitro experiments. Changes in the apoptosis pathway caused by the synergistic effect of H2 and radiotherapy were reported. Guided by its excellent photoacoustic imaging capabilities, mice with orthotopic liver cancer achieved excellent therapeutic effects and low inflammatory side effects, suggesting that Au-TiO2 @ZnS has promising application potential for cancer treatment and prognosis.

Dual Ratiometric SERS and Photoacoustic Core-Satellite Nanoprobe for Quantitatively Visualizing Hydrogen Peroxide in Inflammation and Cancer.

Excessive production of oxidative species alters the normal redox balance and leads to diseases, such as chronic inflammation and cancer. Oxidative species are short-lived species, which makes direct, precise, and real-time measurements difficult. Herein, we report a novel core-satellite gold nanostructure for dual, ratiometric surface-enhanced Raman scattering (SERS) and photoacoustic (PA) imaging to enable the precise detection of inflammation/cancer-related H2 O2 . The combination of H2 O2 -activated second near-infrared (NIR-II) PA imaging and SERS imaging enables the differentiation between the inflamed region and normal tissue with high accuracy. The mesoporous silica shell of the nanoprobe could be used to deliver drugs to the target area to precisely treat disease. Therefore, this core-satellite nanostructure can not only quantitatively and precisely monitor H2 O2 produced in inflammation, tumor, and osteoarthritis in rabbits in real-time, but can also be used to track the progress of the anti-inflammatory treatment in real-time.