Reactive oxygen/nitrogen species scavenging and inflammatory regulation by renal-targeted bio-inspired rhodium nanozymes for acute kidney injury theranostics.

Acute kidney injury (AKI) results from the rapid deterioration of renal function, which is mainly treated by transplantation and dialysis, and has a high mortality rate. Inflammation induced by excess reactive oxygen/nitrogen species (RONS) plays a crucial role in AKI. Although small molecule antioxidants have been utilized to alleviate AKI, low bioavailability and side-effect of these drugs tremendously limit their clinical use. Hence, we successfully construct ultra-small (2-4 nm) rhodium nanoparticles modified with l-serine (denoted as Rh-Ser). Our results show that Rh-Ser with multiple enzyme-mimicking activities, allows remove various RONS to protect damaged kidney cells. Additionally, the ultrasmall size of Rh-Ser is conducive to enrichment in the renal tubules, and the modification of l-serine enables Rh-Ser to bind to kidney injury molecule-1, which is highly expressed on the surface of damaged renal cells, thereby targeting the damaged kidney and increasing the retention time. Moreover, Rh-Ser allows the production of oxygen at the inflammatory site, thus further improving hypoxia and inhibiting pro-inflammatory macrophages to relieve inflammation, and increasing the survival rate of AKI mice from 0 to 80%, which exhibits a better therapeutic effect than that of small molecule drug. Photoacoustic and fluorescence imaging can effectively monitor and evaluate the enrichment and therapeutic effect of Rh-Ser. Our study provides a promising strategy for the targeted treatment of AKI via RONS scavenging and inflammatory regulation.

Biodegradable Osmium Nanoantidotes for Photothermal-/Chemo- Combined Treatment and to Prevent Chemotherapy-Induced Acute Kidney Injury.

Acute kidney injury (AKI) is a common adverse event in chemotherapy patients. AKI is accompanied by the generation of reactive oxygen species (ROS) and inflammation. Therefore, the management of ROS and inflammation is a potential strategy for AKI mitigation. Herein, polyethylene glycol-coated osmium nanozyme-based antidotes (Os) are developed for imaging-guided photothermal therapy (PTT) in combination with cisplatin (Pt); while, avoiding AKI induced by high-dose Pt. Os nanoantidotes can enhance the efficiency of tumor treatment during combined PTT and chemotherapy and inhibit tumor metastasis by improving the hypoxic and inflammatory tumor microenvironment. Os nanoantidotes preferentially accumulate in the kidney because of their 2-nm size distribution; and then, regulate inflammation by scavenging ROS and generating oxygen to alleviate Pt-induced AKI. Os nanoantidotes can be cleared from the kidneys by urine excretion but can be degraded under hydrogen peroxide stimulation, reducing the bio-retention of these compounds. By integrating PTT with inflammatory regulation, Os nanoantidotes have the potential to reduce the side effects of chemotherapy, offering an alternative route for the clinical management of cancer patients with chemotherapy-induced AKI.

Iridium nanozyme-mediated photoacoustic imaging-guided NIR-II photothermal therapy and tumor microenvironment regulation for targeted eradication of cancer stem cells.

Cancer stem cells (CSCs) are found in many solid tumors, which play decisive roles in the occurrence, recurrence and metastasis of tumors. However, drugs are difficult to kill CSCs due to their limited number and location in oxygen-deprived tissue far from the blood vessels. Meanwhile, the survival and stemness maintenance of CSCs strongly depend on the tumor microenvironment (TME). Herein, we developed a CD44 antibody modified iridium nanosheet with enzyme-like activity (defined as Ir Nts-Ab) that effectively eradicates CSCs for cancer therapy. We observe that Ir Nts-Ab can enrich tumor tissues to remove excessive reactive oxygen species and produce oxygen, thus alleviating hypoxia and the inflammatory TME to reduce the proportion of CSCs and inhibit metastasis. In addition, Ir Nts-Ab targets CSCs and normal cancer cells with near infrared II-region photothermal therapy (NIR-II PTT), and is easily taken up by CSCs due to recognition of the CD44 proteins. Moreover, photoacoustic imaging helps monitor drug accumulation and hypoxic TME improvement in tumor tissue. Importantly, Ir Nts-Ab has good biological safety, making it suitable for biomedical applications. This iridium nanozyme based on TME regulation as well as NIR-II PTT will be a promising strategy for the treatment of cancer. STATEMENT OF SIGNIFICANCE: Cancer stem cells (CSCs) are key factors that make tumors difficult to eradicate, and strongly depend on the hypoxic tumor microenvironment (TME), which plays a crucial role in the occurrence and metastasis of tumors. Herein, an antibody modified iridium nanosheet (definition as Ir Nts-Ab) was developed for targeted eradication of CSCs by photoacoustic imaging guided photothermal therapy (PTT) and TME regulation. Ir Nts-Ab with catalase-like activity could inhibit HIF-1α by producing oxygen, thus effectively reducing the proportion of CSCs and inhibiting tumor metastasis. Additionally, Ir Nts-Ab achieved the eradication of CSCs by PTT, and eliminated reactive oxygen species to decrease the inflammatory response, resulting in reduced tumor metastasis, which was promising for the cure of solid tumors in the clinics.

Nacre-inspired, strong, tough silk fibroin hydrogels based on biomineralization and the layer-by-layer assembly of ordered silk fabric.

Hydrogels are attractive materials with structures and functional properties similar to biological tissues and widely used in biomedical engineering. However, traditional synthetic hydrogels possess poor mechanical strength, and their applications are limited. Herein, a multidimensional material design method is developed; it includes the in situ gelation of silk fabric and nacre-inspired layer-by-layer assembly, which is used to prepare silk fibroin (SF) hydrogels. The in situ gelation method of silk fabric introduces a directionally ordered fabric network in a silk substrate, considerably enhancing the strength of hydrogels. Based on the nacre structure, the layer-by-layer assembly method enables silk hydrogels to break through the size limit and increase the thickness, realizing the longitudinal extension of the hydrogels. The application of the combined biomineralization and hot pressing method can effectively reduce interface defects and improve the interaction between organic and inorganic interfaces. The multidimensional material design method helps increase the strength (287.78 MPa), toughness (18.43 MJ m-3), and fracture energy (50.58 kJ m-2) of SF hydrogels; these hydrogels can weigh 2000 times their own weight. Therefore, SF hydrogels designed using the aforementioned combined method can realize the combination of strength and toughness and be used in biological tissue engineering and structural materials.

Activation of the cGAS-STING pathway by a mitochondrial DNA-targeted emissive rhodium(iii) metallointercalator.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) pathway is a key mediator of innate immunity involved in cancer development and treatment. The roles of mitochondrial DNA (mtDNA) in cancer immunotherapy have gradually emerged. Herein, we report a highly emissive rhodium(iii) complex (Rh-Mito) as the mtDNA intercalator. Rh-Mito can specifically bind to mtDNA to cause the cytoplasmic release of mtDNA fragments to activate the cGAS-STING pathway. Moreover, Rh-Mito activates the mitochondrial retrograde signaling by disturbing the key metabolites involved in epigenetic modifications, which alters the nuclear genome methylation landscape to influence the expression of genes related to immune signaling pathways. Finally, we demonstrate that ferritin-encapsulated Rh-Mito elicits potent anticancer activities and evokes intense immune responses in vivo by intravenous injection. Overall, we report for the first time that small molecules targeting mtDNA can activate the cGAS-STING pathway, which gives insights into the development of biomacromolecule-targeted immunotherapeutic agents.

Tantalum Nitride-Based Theranostic Agent for Photoacoustic Imaging-Guided Photothermal Therapy in the Second NIR Window.

Metal nitrides show excellent photothermal stability and conversion properties, which have the potential for photothermal therapy (PTT) for cancer. Photoacoustic imaging (PAI) is a new non-invasive and non-ionizing biomedical imaging method that can provide real-time guidance for precise cancer treatment. In this work, we develop polyvinylpyrrolidone-functionalized tantalum nitride nanoparticles (defined as TaN-PVP NPs) for PAI-guided PTT of cancer in the second near-infrared (NIR-II) window. The TaN-PVP NPs are obtained by ultrasonic crushing of massive tantalum nitride and further modification by PVP to obtain good dispersion in water. Due to their good absorbance in the NIR-II window, TaN-PVP NPs with good biocompatibility have obvious photothermal conversion performance, realizing efficient tumor elimination by PTT in the NIR-II window. Meanwhile, the excellent PAI and photothermal imaging (PTI) capabilities of TaN-PVP NPs are able to provide monitoring and guidance for the treatment process. These results indicate that TaN-PVP NPs are qualified for cancer photothermal theranostics.

Cartilage structure-inspired elastic silk nanofiber network hydrogel for stretchable and high-performance supercapacitors.

Flexible supercapacitors are an important portable energy storage but suffer from low capacitance, inability to stretch, etc. Therefore, flexible supercapacitors must achieve higher capacitance, energy density, and mechanical robustness to expand the applications. Herein, a hydrogel electrode with excellent mechanical strength was created by simulating the collagen fiber network and proteoglycan in cartilage using silk nanofiber (SNF) network and polyvinyl alcohol (PVA). The Young's modulus and breaking strength of the hydrogel electrode increased by 205 % and 91 % compared with PVA hydrogel owing to the enhanced effect of the bionic structure, respectively, which are 1.22 MPa and 1.3 MPa. The fracture energy and fatigue threshold reached 1813.5 J/m2 and 1585.2 J/m2, respectively. The SNF network effectively connected carbon nanotubes (CNTs) and polypyrrole (PPy) in series, affording a capacitance of 13.62 F/cm2 and energy density of 1.2098 mWh/cm2. This capacitance is the highest among currently reported PVA hydrogel capacitors, which can maintain >95.2 % after 3000 charge-discharge cycles. This capacitance Notably, the cartilage-like structure endowed the supercapacitor with high resilience; thus, the capacitance remained >92.1 % under 150 % deformation and >93.35 % after repeated stretching (3000 times), which was far superior to that of other PVA-based supercapacitors. Overall, this effective bionic strategy can endow supercapacitors with ultrahigh capacitance and effectively ensure the mechanical reliability of flexible supercapacitors, which will help expand the applications of supercapacitors.

Self-Assembled Carrier-Free Nanodrugs for Starvation Therapy-Amplified Photodynamic Therapy of Cancer.

Traditional starvation treatment strategies, which involve glucose oxidase and drug-induced thrombi, often suffer from aggravated tumor hypoxia and have failed to improve antitumor efficacy in combination with oxygen-dependent photodynamic therapy (PDT). Herein, glucose transporter 1 inhibitor genistein (Gen) and photosensitizer chlorin e6 (Ce6) are integrated to construct carrier-free self-assembled nanoparticles defined as GC NPs, for starvation therapy-amplified PDT of tumor. GC NPs with regular morphology and stability are screened out by component adjustment, while the function of each component is preserved. On the one hand, Gen released from GC NPs can cut off tumor glucose uptake by inhibiting the glucose transporter 1 to restrict tumor growth, achieving starvation therapy. On the other hand, they are able to decrease the amount of oxygen consumed by tumor respiration and amplify the therapeutic effect of PDT. In vitro and in vivo experiments verify the excellent synergistic antitumor therapeutic efficacy of GC NPs without any apparent toxicity. Moreover, fluorescence and photoacoustic imaging provide guidance for in vivo PDT, demonstrating the excellent tumor enrichment efficiency of GC NPs. It is believed that this starvation therapy-amplified PDT strategy by carrier-free self-assembled GC NPs holds promising clinical prospects.

An all-cellulose sponge with a nanofiller-assisted hierarchical cellular structure for fruit maintaining freshness.

Cellulose sponges with compressibility and resilience are an ideal packaging material for fruits with fragile skin. Here, a soft and elastic all-cellulose sponge (CS) with a hierarchical cellular structure was fabricated, where the long molecular chain cellulose constructed major pores, the cellulose at nanoscale acted as an elastic nanofiller to fill the gaps of long molecular chain cellulose fibers and constructed minor pores. With these two kinds of pores, this structure can absorb strain hierarchically. The sponge can protect fruits from mechanical damage when dropped or repeated vibration. Furthermore, the CS modified with chlorogenic acid (C-CGAS) had excellent antibacterial and antifungal abilities. Therefore, C-CGAS could extend the storage time of strawberries to 18 days without any microbial invasion, which is the longest storage time reported thus far. This study provides a new idea for the preparation of polymer sponges and a new design for the development of antimicrobial packaging materials.

Iridium Tungstate Nanozyme-Mediated Hypoxic Regulation and Anti-inflammation for Duplex Imaging Guided Photothermal Therapy of Metastatic Breast Tumors.

Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.

Plasma arginase-1 as a predictive marker for early transarterial chemoembolization refractoriness in unresectable hepatocellular carcinoma.

Objective: To explore the relationship between plasma arginase-1 (ARG1) and early transarterial chemoembolization (TACE) refractoriness in patients with hepatocellular carcinoma (HCC) and develop nomograms for predicting early TACE refractoriness. Methods: A total of 200 patients with HCC, treated with TACE, were included in the study, including 120 in the training set and 80 in the validation set. Pre-treatment enzyme-linked immunosorbent assay was used to detected the plasma ARG1 levels of the patient, and independent predictors of early TACE refractoriness were determined using a multivariate logistic regression model, based on which a predictive model was developed using a nomogram. Results: Risk of early TACE refractoriness was negatively correlated with plasma ARG1 levels, and multivariate logistic analysis showed tumour size (OR = 1.138, 95% CI = 1.006-1.288, P = 0.041), multiple tumors (OR=4.374, 95% CI = 1.189-16.089, P = 0.026), platelet count (OR = 0.990, 95% CI = 0.980-0.999, P = 0.036), and plasma ARG1 levels (OR = 0.209, 95% CI = 0.079-0.551, P = 0.002) to be independent prognostic factors for early TACE refractoriness.The AUC value for the nomogram of the training cohort was 0.786 (95% CI = 0.702-0.870), and the validation set AUC value was 0.833 (95% CI = 0.791-0.875).The decision curve analysis suggested that the nomogram had good clinical utility. Conclusion: High plasma ARG1 expression was associated with a lower incidence of early TACE refractoriness. The nomogram constructed based on four independent prognostic factors could facilitate an individualised prediction of the incidence of early TACE refractoriness.

Natural phenolics and flavonoids modified the hierarchical cellular cellulose sponges for efficient water disinfection.

Disinfecting microbially contaminated water in a safe and sustainable way is a great challenge. The phenolics and flavonoids in plants are ideal antibacterial agents for biosafety. Herein, an all-plant-derived antibacterial sponge with a hierarchical cellular structure was prepared from natural phenolic and flavonoid crude extracts and cellulose for water purification. After being modified by quercetin, the quercetin-cellulose sponge (Q-CS) exhibits great toughness, elasticity and a large specific surface area, which benefited from a unique hierarchical cellular structure. Q-CS shows ultrahigh water flux (4.5 × 105 L·m-2·h-1·bar-1) and excellent antibacterial abilities against Escherichia coli and Staphylococcus aureus (<1.87 % viability). Sponges modified with crude pyrola (P-CS) and mulberry leaf extracts (M-CS) have similar properties compared with Q-CS. The good performances of P-CS and M-CS show the strong antibacterial applications of natural crude extract. This work provides a strategy for fabricating sustainable and safe antibacterial sponges for water disinfection.

Evaluation of the Chemical Composition and Antioxidant Activity of Mulberry (Morus alba L.) Fruits from Different Varieties in China.

Mulberry (Morus alba L.) fruit is a fruit with nutritional and medicinal value. It is widely cultivated in different regions of China, which may result in differences in its chemical composition. In this research, 25 mulberry fruit samples from six provinces in China were investigated. The contents of anthocyanins were evaluated by high-performance liquid chromatography (HPLC). The contents of two main anthocyanins, cyanidin-3-O-glucoside (C3G) and cyanidin-3-O-rutinoside (C3R), ranged from 0.656 ± 0.006 mg/g to 4.367 ± 0.243 mg/g and from 0.226 ± 0.007 mg/g to 1.649 ± 0.013 mg/g, respectively. Additionally, the contents of total phenolic, total flavonoid, vitamin C, titratable acids, reducing sugars and antioxidant capacity (FRAP, DPPH, scavenging and hydroxyl radical scavenging activity) were also assessed. The results and principal component analysis showed that the Zhongsang 5801 variety from Sichuan, Dechang had the greatest health value with the highest active compound contents. Based on our analysis, the variety from Sichuan, Dechang is a high-quality plant source for mulberry fruit cultivation. This research provides a basis for the rational development and utilization of mulberry fruit resources in China.

Soft and elastic silver nanoparticle-cellulose sponge as fresh-keeping packaging to protect strawberries from physical damage and microbial invasion.

Strawberry is a nutritious food that is susceptible to mechanical injury and microbiological infection. Traditional coatings for strawberry packaging provide resistance against microbial infection but not against mechanical damage. In this study, a soft and elastic cellulose sponge modified with silver nanoparticles (AgNPs@CS-1:1) was prepared as strawberry packaging material, and it provided effective protection against mechanical damage. In addition, after 1000 cyclic compression, AgNPs@CS-1:1 presented only 16.80% unrecoverable deformation and still had elasticity, suggesting its fatigue resistance and durable protection for strawberry against damage caused by repeated vibrations during transportation. In addition, AgNPs@CS-1:1 had good antibacterial (E. coli and S. aureus) and antifungal (Rhizopus stolonifer) abilities. The storage time of strawberries packaged by AgNPs@CS-1:1 was extended to 12 days without microbial invasion. Thus, AgNPs@CS-1:1 provided dual protection at the physical and microbial levels. This study proposes a new method for the preservation of strawberries based on the utilization of cellulose.

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury.

Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.

In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy.

Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy.

Bioactive NIR-II Light-Responsive Shape Memory Composite Based on Cuprorivaite Nanosheets for Endometrial Regeneration.

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near-infrared (NIR-II) light-responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4 O10 ) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l-lactide-co-trimethylene carbonate) (PT) as shape memory building blocks is developed. The as-prepared CUP/PT composite possesses excellent shape memory performance under NIR-II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.

In-situ TiO2-x decoration of titanium carbide MXene for photo/sono-responsive antitumor theranostics.

BACKGROUND: Sonodynamic therapy (SDT) has emerged as a noninvasive therapeutic modality that involves sonosensitizers and low-intensity ultrasound. However, owing to the rapid recombination of charge carriers, most of the sonosensitizers triggered poor reactive oxygen species (ROS) generation, resulting in unsatisfactory sonodynamic therapeutic effects. RESULTS: Herein, a photo/sono-responsive nanoplatform was developed through the in-situ systhesis of TiO2-x on the surface of two-dimensional MXene (titanium carbide, Ti3C2) for photoacoustic/photothermal bimodal imaging-guided near-infrared II (NIR-II) photothermal enhanced SDT of tumor. Because of several oxygen vacancies and smaller size (~ 10 nm), the in-situ formed TiO2-x nanoparticles possessed narrow band gap (2.65 eV) and high surface area, and thus served as a charge trap to restrict charge recombination under ultrasound (US) activation, resulting in enhanced sonodynamic ROS generation. Moreover, Ti3C2 nanosheets induced extensive localized hyperthermia relieves tumor hypoxia by accelerating intratumoral blood flow and tumor oxygenation, and thus further strengthened the efficacy of SDT. Upon US/NIR-II laser dual-stimuli, Ti3C2@TiO2-x nanoplatform triggered substantial cellular killing in vitro and complete tumor eradication in vivo, without any tumor recurrence and systemic toxicity. CONCLUSION: Our work presents the promising design of photo/sono-responsive nanoplatform for cancer nanotheranostics.

Clinically translatable gold nanozymes with broad spectrum antioxidant and anti-inflammatory activity for alleviating acute kidney injury.

Rationale: Acute kidney injury (AKI) is associated with aberrant generation of oxidative species and inflammation, leading to high mortality of in-hospitalized patients. Although N-acetylcysteine (NAC) showed positive effects in alleviating contrast-induced AKI, the clinical applications are strongly restrained due to the low bioavailability, low renal accumulation, short renal retention time, and high dosage-induced toxicity. Methods: We addressed the clinical dilemma of NAC by developing ultrasmall gold nanoclusters (1-2 nm) capped with NAC (denoted as Au NCs-NAC) as a nanozyme-based antioxidant defense system for AKI alleviation. Rhabdomyolysis-induced AKI mice model was developed, and the same dose of free NAC (as a control) and NAC onto Au NCs (Au NCs-NAC) was used for in vivo investigation of AKI restoration. Results: The as-developed gold nanozyme exhibited high bioavailability and good physicochemical stability as compared to NAC. Meanwhile, Au NCs-NAC showed broad-spectrum antioxidant activity of Au NCs-NAC, offering in vitro renoprotective effects, as well as macrophages by relieving inflammation under hydrogen peroxide or lipopolysaccharide stimulation. Notably, owing to the smaller size than kidney threshold (5.5 nm), Au NCs-NAC displayed preferential renal enrichment (< 2 h) and longer retention (> 24 h) in AKI mice as revealed by fluorescence imaging, thereby largely enhancing the restoration of renal function in AKI mice than free NAC by protecting the kidneys from oxidative injury and inflammation without systemic toxicity, as demonstrated by tissues staining, inflammatory cytokines and biomarkers detection, and mice survival rate. Conclusion: Owing to the synergistic anti-inflammatory/antioxidative effects, and enhanced bioavailability and renal accumulation/retention, Au NCs-NAC displayed far superior therapeutic performance than NAC alone. This work will facilitate the development of high-performance antioxidative nanoplatforms, as well as overcome the clinical limitations of small molecular drugs for AKI treatment and other inflammatory diseases.

Prussian blue-based theranostics for ameliorating acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) with high mortality rates is associated with an excess of reactive oxygen/nitrogen species (RONS) within kidney tissues. Recently, nanomedicine antioxidant therapy has been used to alleviate AKI. Herein, we synthesized ultrasmall Prussian blue nanozymes (PB NZs, 4.5 nm) as theranostic agents for magnetic resonance (MR)/photoacoustic (PA) dual-modal imaging guided AKI treatment. RESULTS: PB NZs exhibited multi-enzyme mimetic abilities, promoting the effective elimination of RONS both in vitro and in vivo. Moreover, benefiting from their imaging contrast properties, the rapid renal accumulation of PB NZs was verified by in vivo PA/MR dual-modal imaging. Due to their excellent enrichment in the kidney and unique multi-enzyme mimetic abilities, ultrasmall PB NZs displayed superior AKI treatment efficacy compared with that of amifostine in two clinically relevant types of AKI induced murine models (either by rhabdomyolysis or cisplatin). CONCLUSION: Our findings suggested ultrasmall PB NZs, as nanozyme theranostics, have great potential for AKI management.