Microneedle System with Biomarker-Activatable Chromophore as Both Optical Imaging Probe and Anti-bacterial Agent for Combination Therapy of Bacterial-Infected Wounds and Outcome Monitoring.

Wounds infected with bacteria, if left untreated, have the potential to escalate into life-threatening conditions, such as sepsis, which is characterized by widespread inflammation and organ damage. A comprehensive approach to treating bacterial-infected wounds, encompassing the control of bacterial infection, biofilm eradication, and inflammation regulation, holds significant importance. Herein, a microneedle (MN) patch (FM@ST MN) has been developed, with silk fibroin (SF) and tannic acid-based hydrogel serving as the matrix. Encapsulated within the MNs are the AIEgen-based activatable probe (FQ-H2O2) and the NLRP3 inhibitor MCC950, serving as the optical reporter/antibacterial agent and the inflammation regulator, respectively. When applied onto bacterial-infected wounds, the MNs in FM@ST MN penetrate bacterial biofilms and gradually degrade, releasing FQ-H2O2 and MCC950. The released FQ-H2O2 responds to endogenously overexpressed reactive oxygen species (H2O2) at the wound site, generating a chromophore FQ-OH which emits noticeable NIR-II fluorescence and optoacoustic signals, enabling real-time imaging for outcome monitoring; and this chromophore also exhibits potent antibacterial capability due to its dual positive charges and shows negligible antibacterial resistance. However, the NLRP3 inhibitor MCC950, upon release, suppresses the activation of NLRP3 inflammasomes, thereby mitigating the inflammation triggered by bacterial infections and facilitating wound healing. Furthermore, SF in FM@ST MN aids in tissue repair and regeneration by promoting the proliferation of epidermal cells and fibroblasts and collagen synthesis. This MN system, free from antibiotics, holds promise as a solution for treating and monitoring bacterially infected wounds without the associated risk of antimicrobial resistance.

Homo-Dyad with Outer Hydration Layer Approach for Developing NIR-II Chromophore of High Stability and Water-Solubility as Injectable and Sprayable Optical Probe.

Dyes with extended conjugate structures are the focus of extensive design and synthesis efforts, aiming to confer unique and improved optical and electronic properties. Such advancements render these dyes applicable across a wide spectrum of uses, ranging from second-window near-infrared (NIR-II) bioimaging to organic photovoltaics. Nevertheless, the inherent benefits of long conjugation are often accompanied by persistent challenges like aggregation, fluorescence quenching, absorption blueshift, and low stability and poor water solubility. Herein, a unique structural design strategy termed "homo-dyad with outer hydration layer" is introduced to address these inherent problems, tailored for the development of imaging probes exhibiting long absorption/emission wavelengths. This approach involves bringing two heptamethine cyanines together through a flexible linker, forming a homo-dyad structure, while strategically attaching four polyethylene glycol (PEG9) chains to the terminal heterocycles. This approach imparts excellent water solubility, biocompatibility, and enhanced chemical, photo-, and spectral stability for the dyes. Utilizing this strategy, a biomarker-activatable probe (HD-FL-4PEG9-N) for NIR-II fluorescent and 3D multispectral optoacoustic tomography imaging is developed, and its effectiveness in disease visualization. It can not only serve as an injectable probe for acute kidney injury imaging due to its high water solubility, but also a sprayable probe for imaging bacterial-infected wounds.

Injectable-Hydrogel-Based Tissue Sealant for Hemostasis, Bacteria Inhibition, and Pro-Angiogenesis in Organ Bleeding Wounds and Therapeutic Outcome Monitoring Via NIR-II Optical Imaging.

Sudden hemorrhage stemming from internal organ wounds poses a grave and potentially fatal risk if left untreated. Injectable-hydrogel-based tissue sealants featuring multiple actions, including fit-to-shape in situ gelation, rapid hemostasis, pro-angiogenic, anti-bacterial and outcome tracking, are ideal for the management of organ trauma wounds. Herein, an injectable-hydrogel tissue sealant AN@CD-PEG&TQ which consists of four-arm 4-arm poly(ethylene glycol) (PEG-SC) succinimidyl carbonate), AN@CD nanoprobe, and two bioactive peptides (anti-microbial peptide Tet213 and pro-angiogenic peptide QK) is developed. Among them, AN@CD nanoparticles form through host/guest complexation of amino-group-containing ß-cyclodextrin and adamantyl group, enabling in situ biomarker (NO)-activatable optoacoustic/NIR-II: Near-infrared second biological window fluorescent imaging. The ample ─NH2 groups on the surface of AN@CD readily engage in rapid cross-linking with succinimidyl ester groups located at the ends of four-arm PEG-SC. This cross-linking expedites the gelation process without necessitating additional initiators or cross-linking agents; thus, significantly enhancing both hydrogel's application convenience and biocompatibility. Bioactive peptides (Tet213 and QK) safeguard against possible bacterial infections, facilitate angiogenesis, and eventually, improve organ wounds healing. This hydrogel-based tissue sealant demonstrates superior therapeutic and bioimaging performance in various mouse models including liver hemorrhage, gastric perforation, and bacterial-infected skin wound mouse models, highlighting its potential as a high-performance wound sealant for organ bleeding wound management.

Visualization detection of mycotoxin patulin in fruit juices by a small-molecule fluorescent probe.

The mycotoxin patulin is a common contaminant in rotten fruits, posing severe food safety risks and threats to human health. Developing a convenient, sensitive and reliable method for patulin detection is of utmost importance but remains challenging. In this study, we have successfully designed and synthesized a small-molecule fluorescent probe, FITC-Lys, which demonstrates good sensitivity in detecting patulin. Upon contact with patulin, the terminal Lys group of the FITC-Lys probe reacts with patulin, resulting in the formation of the fluorescein dimer that subsequently quenches fluorescence. This variation of fluorescence enables the visualization and sensitive detection of patulin. The probe exhibits good sensitivity with a low LOD of 8 ng mL-1 for the fluorescence spectrum method and a LOD of 12 ng mL-1 for the fluorescence imaging method. Moreover, we have validated the probe's capability for patulin detection in apple and pear juices, achieving good recoveries ranging from 98.60% to 103.80%. Notably, the probe FITC-Lys is the first small-molecule fluorescent probe that has proven successful in visualizing patulin in juices derived from decayed apples and pears. Consequently, this probe holds great potential as a practical tool for monitoring patulin in foodstuffs, thereby contributing to enhanced food safety standards.

Cucurbit[8]uril-based water-dispersible assemblies with enhanced optoacoustic performance for multispectral optoacoustic imaging.

Organic small-molecule contrast agents have attracted considerable attention in the field of multispectral optoacoustic imaging, but their weak optoacoustic performance resulted from relatively low extinction coefficient and poor water solubility restrains their widespread applications. Herein, we address these limitations by constructing supramolecular assemblies based on cucurbit[8]uril (CB[8]). Two dixanthene-based chromophores (DXP and DXBTZ) are synthesized as the model guest compounds, and then included in CB[8] to prepare host-guest complexes. The obtained DXP-CB[8] and DXBTZ-CB[8] display red-shifted and increased absorption as well as decreased fluorescence, thereby leading to a substantial enhancement in optoacoustic performance. Biological application potential of DXBTZ-CB[8] is investigated after co-assembly with chondroitin sulfate A (CSA). Benefiting from the excellent optoacoustic property of DXBTZ-CB[8] and the CD44-targeting feature of CSA, the formulated DXBTZ-CB[8]/CSA can effectively detect and diagnose subcutaneous tumors, orthotopic bladder tumors, lymphatic metastasis of tumors and ischemia/reperfusion-induced acute kidney injury in mouse models with multispectral optoacoustic imaging.

Renal-Clearable Probe with Water Solubility and Photostability for Biomarker-Activatable Detection of Acute Kidney Injuries via NIR-II Fluorescence and Optoacoustic Imaging.

Acute kidney injuries (AKI) have serious short-term or long-term complications with high morbidity and mortality rate, thus posing great health threats. Developing high-performance NIR-II probes for noninvasive in situ detection of AKI via NIR-II fluorescent and optoacoustic dual-mode imaging is of great significance. Yet NIR-II chromophores often feature long conjugation and hydrophobicity, which prevent them from being renal clearable, thus limiting their applications in the detection and imaging of kidney diseases. To fully exploit the advantageous features of heptamethine cyanine dye, while overcoming its relatively poor photostability, and to strive to design a NIR-II probe for the detection and imaging of AKI with dual-mode imaging, herein, we have developed the probe PEG3-HC-PB, which is renal clearable, water soluble, and biomarker activatable and has good photostability. As for the probe, its fluorescence (900-1200 nm) is quenched due to the existence of the electron-pulling phenylboronic group (responsive element), and it exhibits weak absorption with a peak at 830 nm. Meanwhile, in the presence of the overexpressed H2O2 in the renal region in the case of AKI, the phenylboronic group is converted to the phenylhydroxy group, which enhances NIR-II fluorescent emission (900-1200 nm) and absorption (600-900 nm) and eventually produces conspicuous optoacoustic signals and NIR-II fluorescent emission for imaging. This probe enables detection of contrast-agent-induced and ischemia/reperfusion-induced AKI in mice using real-time 3D-MSOT and NIR-II fluorescent dual-mode imaging via response to the biomarker H2O2. Hence, this probe can be used as a practicable tool for detecting AKI; additionally, its design strategy could provide insight into the design of other large-conjugation NIR-II probes with multifarious biological applications.

A biomarker-responsive nanoprobe for detecting hepatic ischemia-reperfusion injury via optoacoustic/NIR-II fluorescence imaging.

A nanoprobe for detecting hepatic ischemia-reperfusion injury has been developed. Apparent optoacoustic and NIR-II fluorescent signals are given out upon the nanoprobe's response to the in situ biomarker H2O2 in the liver in the case of ischemia-reperfusion injury.

Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from -4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.

An NO-responsive probe for detecting acute inflammation using NIR-II fluorescence/optoacoustic imaging.

An NO-responsive probe for imaging acute inflammation was developed. The probe responds to in situ NO in acute inflammation sites such as LPS-induced acute dermatitis and MIA-induced acute joint inflammation with turn-on NIR-II fluorescence and optoacoustic signals.

Water-Dispersible Activatable Nanoprobe for Detecting Cadmium-Ion-Induced Oxidative Stress in Edible Crops via Near-Infrared Second-Window Fluorescence Imaging.

Edible crops are important in terms of food security and sustainable agriculture. Heavy-metal-ion contamination of water/soil has deleterious impacts on the growth of edible crops. Among the heavy metals, cadmium (Cd) is toxic to plants, people, and animals, as it is widely used in industry; it has become the most important metal ion in the soil/water pollution. Once the toxic Cd ion enters edible crops via the water/soil in which the crops grow, it will induce oxidative stress (overproduction of reactive oxygen species with H2O2 being the most abundant) in the crops, and strong oxidative stress leads to the crops' growth depression or inhibition. Hence, it is of great significance to accurately monitor the oxidative stress induced by Cd ions in edible crops, as the monitoring results could be employed for the early warning of Cd-ion pollution in water/soil. Herein, we design an activatable nanoprobe that can detect Cd-ion-induced oxidative stress in edible crops via near-infrared second-window (NIR-II) fluorescence imaging. The molecular probe IXD-B contains the diphenylamine-modified xanthene group acting as the electron-donating unit, bis(methylenemalononitrile)indan as the electron-accepting unit, and the methenephenylboronic acid group as the recognition moiety for H2O2 and the fluorescence quencher. The probe molecules being encapsulated by the amphiphilic DSPE-PEG2000 render the water-dispersible nanoprobe (IXD-B@DSPE-PEG2000). When the nanoprobe enters the edible crops, it can be activated by the overexpressed H2O2 therein and consequently emit strong NIR-II fluorescence signals for visualizing and tracking the oxidative stress in edible crops induced by Cd ions.

A Biomarker-Responsive Nanosystem with Colon-Targeted Delivery for Ulcerative Colitis's Detection and Treatment with Optoacoustic/NIR-II Fluorescence Imaging.

Ulcerative colitis (UC) is a prevalent idiopathic inflammatory disease which causes such complications as intestinal perforation, obstruction, and bleeding, and thus deleteriously impacting people's normal work and quality of life. Hence, accurate diagnosis of UC is crucial in terms of planning optimal treatment plan. Herein, a pH/reactive oxygen species (ROS) dual-responsive nanosystem (BM@EP) is developed for UC's detection and therapy. BM@EP is composed of a chromophore-drug dyad and the enteric coating. The chromophore-drug dyad (BOD-XT-DHM) is synthesized by linking the chromophore (BOD-XT-BOH) and a flavonoid drug (dihydromyricetin DHM) through boronate ester bond. The enteric coating includes Eudragit S100 and poly(lactic-co-glycolic acid) (PLGA), the former is commonly employed as a pH-dependent polymer coating excipient so as to attain colon-targeted delivery, and the latter has been widely used as an excipient for the controlled-extended release. After oral administration, BM@EP delivers the dyad (BOD-XT-DHM) into the colon and releases the dyad molecules by being triggered by the alkaline pH in t colon, thereafter upon being stimulated by overexpressed H2 O2 in the inflamed colon, the boronate bond in the dyad is broken down and correspondingly the drug DHM is released for UC therapy, simultaneously the chromophore is released for near-infrared second window (NIR-II) fluorescence and optoacoustic imaging for UC diagnosis and recovery evaluation.

Optical molecular imaging and theranostics in neurological diseases based on aggregation-induced emission luminogens.

Optical molecular imaging and image-guided theranostics benefit from special and specific imaging agents, for which aggregation-induced emission luminogens (AIEgens) have been regarded as good candidates in many biomedical applications. They display a large Stokes shift, high quantum yield, good biocompatibility, and resistance to photobleaching. Neurological diseases are becoming a substantial burden on individuals and society that affect over 50 million people worldwide. It is urgently needed to explore in more detail the brain structure and function, learn more about pathological processes of neurological diseases, and develop more efficient approaches for theranostics. Many AIEgens have been successfully designed, synthesized, and further applied for molecular imaging and image-guided theranostics in neurological diseases such as cerebrovascular disease, neurodegenerative disease, and brain tumor, which help us understand more about the pathophysiological state of brain through noninvasive optical imaging approaches. Herein, we focus on representative AIEgens investigated on brain vasculature imaging and theranostics in neurological diseases including cerebrovascular disease, neurodegenerative disease, and brain tumor. Considering different imaging modalities and various therapeutic functions, AIEgens have great potential to broaden neurological research and meet urgent needs in clinical practice. It will be inspiring to develop more practical and versatile AIEgens as molecular imaging agents for preclinical and clinical use on neurological diseases.

Aminopeptidase N Activatable Nanoprobe for Tracking Lymphatic Metastasis and Guiding Tumor Resection Surgery via Optoacoustic/NIR-II Fluorescence Dual-Mode Imaging.

Lymphatic metastasis is a crucial mechanism by which the cancer cells break away from the primary (original) tumor and travel to the closest regional lymph node(s) and ultimately to other organs or parts of the body, which is closely associated with tumor recurrence and reduced survival. Thus, tracking tumor lymphatic metastasis and realizing imaging-guided lymphoma resection surgery is of great significance. In this study, an activatable nanoprobe is developed for precisely tracking lymphatic metastasis of tumors and imaging-guided resection of the primary tumor and metastatic lymphoma. The molecular probe contains tricyanofuran as the electron-accepting unit (electron acceptor), xanthene as the electron-donating unit (electron donor), and alanine as the responsive unit (recognition moiety) for aminopeptidase N, and the probe molecules form the nanoprobe with bovine serum albumin as the matrix. The nanoprobe can respond specifically to aminopeptidase N overproduced in the tumor, thereby transmuting the alanine into an amino group, and correspondingly the nanoprobe is activated. Strong optoacoustic and NIR-II fluorescence signals emitted by the activated nanoprobe can be utilized for visualizing the lymphatic metastasis of tumors. Moreover, the nanoprobe with the aid of three-dimensional multispectral optoacoustic tomography (3D MSOT) imaging can accurately locate the tumor site of lymphatic metastasis, and ultimately, both the primary tumor and the metastatic lymphoma can be excised with resection surgery under the guidance of NIR-II fluorescence imaging.

An activatable probe for detection and therapy of food-additive-related hepatic injury via NIR-II fluorescence/optoacoustic imaging and biomarker-triggered drug release.

Food additives are essential to guarantee processed foods' safety throughout its journey from workshops or factories to shops or catering establishment and eventually to consumers. As one of the commonly-used food additives, nitrites upon reaction with amines would generate highly toxic nitrosamines (e.g., N,N-diethylnitrosamine, DEN) as inadvertent byproducts resulted from food processing or preparation which are known to cause hepatotoxicity and even cancer. Hence detecting nitrosamine-induced acute liver injury accurately would be conducive to planning optimal treatment and avoid any further deterioration. Herein we design an activatable probe (BHC-Lut) that can release the drug luteolin for therapy and the chromophore (BHC-OH) for NIR-II fluorescence/optoacoustic imaging upon being triggered by hepatic biomarker hydrogen peroxide. In the probe BHC-Lut, benzoindolium heptamethine cyanine with NIR-II fluorescent emission is adopted as the chromophore scaffold, the incorporation of triethylene glycol into benzoindolium ensures sufficient water solubility and enhances biocompatibility of the probe, and luteolin is coupled onto the chromophore via boronate linkage that acts as both H2O2-responsive unit and the fluorescence quencher. The probe itself is weakly emissive. In the presence of H2O2, the boronate bond is cleaved, and the chromophore BHC-OH and the drug luteolin are released, which produces evident NIR-II fluorescent/optoacoustic signals for imaging and wields therapeutic effect respectively. The probe BHC-Lut has been used in DEN-induced hepatic injury model in mice, and the results evince BHC-Lut's capability for in-situ biomarker-activatable detection and imaging of the acute liver injury site as well as in-situ biomarker-triggered drug release for therapy.

An AIEgen-based oral-administration nanosystem for detection and therapy of ulcerative colitis via 3D-MSOT/NIR-II fluorescent imaging and inhibiting NLRP3 inflammasome.

Ulcerative colitis is the most prevalent forms of inflammatory bowel diseases and a refractory autoimmune disease and affects millions of people worldwide. Herein, we develop an oral-administration nanosystem (QM@EP) for colitis detection, targeted drug delivery/release to colon and therapy. QM@EP consists of a molecular probe QY-SN-H2O2, a NLRP3 inhibitor MCC950 and enteric polymers. QY-SN-H2O2 is based on the AIE-active chromophore QY-SN-OH with pentafluorobenzenesulfonate moieties as the recognition moiety for the biomarker H2O2 and the fluorescence quencher. H2O2 can cleave the pentafluorobenzenesulfonate moieties in QY-SN-H2O2 and thus generating the AIE-active chromophore Q-SN-OH. Two biocompatible polymers were employed in the nanosystem, in which poly(lactic-co-glycolic acid) (PLGA) serves as the sustained release excipient and the Eudragit® S100 acts as the excipient for controlled release of drug formulations in colonic pH to prevent premature drug release in stomach. Our experiments demonstrate that, upon oral administration the nanosystem effectively delivers the probe and drug into colon and release them therein upon being triggered by colonic pH. Then the released probe is activated and turned into the AIE-active chromophore upon being triggered by the pathological level of colonic ROS, thereby bringing about strong fluorescence and optoacoustic signals for NIR-II fluorescence and 3D multispectral optoacoustic tomography (MSOT) imaging for diagnosis and therapeutic outcome monitoring; and the released drug exerts high therapeutic efficacy against ulcerative colitis through inhibiting NLRP3 inflammasome formation.

Rational design of stable heptamethine cyanines and development of a biomarker-activatable probe for detecting acute lung/kidney injuries via NIR-II fluorescence imaging.

Developing high-quality dyes to construct activatable probes for analyte sensing via NIR-II fluorescence is critical for attaining enhanced imaging depths and resolution. Heptamethine cyanines can serve this purpose; however, they usually have poor stability and a tendency to self-aggregate. Herein, we present a design strategy involving the installation of pyridinium and tert-butyl groups onto the central cyclohexenyl core to increase steric crowding, enhance water solubility, and provide a site for the incorporation of analyte-responsive elements. The resulting NP-N dyes emit NIR-II light and can outperform benchmark heptamethine cyanines such as ICG. Using HP-N1, we developed HP-H2O2 and showed that NIR-II fluorescence signals could be enhanced when treating with H2O2. HP-H2O2 was subsequently evaluated in murine models of acute lung injury and acute kidney injury. This strategy unlocks the potential of heptamethine cyanines and is applicable to examples with extended conjugation.

Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways.

Immune-mediated inflammatory diseases (IMIDs) represent a diverse group of diseases and challenges remain for the current medications. Herein, we present an activatable and targeted nanosystem for detecting and imaging IMIDs foci and treating them through blocking NF-κB/NLRP3 pathways. A ROS-activatable prodrug BH-EGCG is synthesized by coupling a near-infrared chromophore with the NF-κB/NLRP3 inhibitor epigallocatechin-3-gallate (EGCG) through boronate bond which serves as both the fluorescence quencher and ROS-responsive moiety. BH-EGCG molecules readily form stable nanoparticles in aqueous medium, which are then coated with macrophage membrane to ensure the actively-targeting capability toward inflammation sites. Additionally, an antioxidant precursor N-acetylcysteine is co-encapsulated into the coated nanoparticles to afford the nanosystem BH-EGCG&NAC@MM to further improve the anti-inflammatory efficacy. Benefiting from the inflammation-homing effect of the macrophage membrane, the nanosystem delivers payloads (diagnostic probe and therapeutic drugs) to inflammatory lesions more efficiently and releases a chromophore and two drugs upon being triggered by the overexpressed in-situ ROS, thus exhibiting better theranostic performance in the autoimmune hepatitis and hind paw edema mouse models, including more salient imaging signals and better therapeutic efficacy via inhibiting NF-κB pathway and suppressing NLRP3 inflammasome activation. This work may provide perceptions for designing other actively-targeting theranostic nanosystems for various inflammatory diseases.

A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging.

Developing high-quality NIR-II fluorophores (emission in 1000-1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.

A Targeted Nanosystem for Detection of Inflammatory Diseases via Fluorescent/Optoacoustic Imaging and Therapy via Modulating Nrf2/NF-κB Pathways.

Inflammatory diseases are sometimes devastating and notoriously difficult to treat. Precisely modulating inflammatory signaling pathways is a promising approach for treating inflammatory diseases. Herein, a multifunctional nanosystem is developed for active targeting, activatable imaging and on-demand therapy against inflammatory diseases through modulating inflammatory pathways. A chromophore-drug dyad (QBS-FIS) is synthesized by linking a chromophore and a Nrf2 (nuclear factor E2-related factor) activator fisetin through boronate bond which serves as fluorescence quencher and ROS (reactive oxygen species)-responsive linker. QBS-FIS molecules form nanoparticles in water and are coated with macrophage cell membrane to ensure active targeting toward inflammation site. To further improve therapeutic efficacy, a NF-kB (nuclear-factor kappa-light-chain-enhancer of activated B cells) inhibitor thalidomide is co-encapsulated to afford the nanosystem (QBS-FIS&Thd@MM). Upon administration into mice, the nanosystem migrates to inflammatory site and pathological ROS therein cleaves the boronate bonds, thereby activating the chromophore for imaging liver/kidney inflammatory diseases for disease diagnosis and recovery evaluation via fluorescence and optoacoustic imaging as well as releasing the active drugs for treating acute liver inflammation through activating Nrf2 pathway and inhibiting NF-kB pathway. The 3D multispectral optoacoustic tomography imaging is applied to precisely locate the inflammatory foci in a spatiotemporal manner.

ALP-activated probe for diagnosis of liver injury by multispectral optoacoustic tomography.

In this chapter, we highlight the advantages of multispectral optoacoustic tomography (MSOT) technique and the activatable photoacoustic probes in the biomedical field, and give a brief introduction to enzyme-activated probes for disease diagnosis and therapeutic outcome evaluation. We also present a detailed description of the procedures for the synthesis of an activatable small molecule probe C1X-OR1 and confirmation of its specific response to alkaline phosphatase in solution and cells. With MSOT, the liposomal C1X-OR1 can be utilized for detection of hepatic ALP as well as for in vivo diagnosis of drug-induced liver injury in a three-dimensional manner.