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Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to abundant reactive oxygen species (ROS). Owing to the multi-enzymatic activity and broad-spectrum ROS scavenging capacity of ceria nanoparticles (ceria NPs), herein, we report ultrasmall citric acid modified ceria nanozymes (3−4 nm) as antioxidants to alleviate rhabdomyolysis-induced AKI through removing excessive ROS. The as-prepared ceria NPs exhibited multi-enzymatic properties such as peroxidase, catalase, and superoxide dismutase, offering efficient protection of renal cells against H 2 O 2 stimulation in vitro. Moreover, due to their ultrasmall size, ceria NPs could efficiently accumulate in the kidneys, thus protecting renal cells against ROS in vivo. Our results present ultrasmall ceria nanozymes as antioxidants for rhabdomyolysisinduced AKI alleviation, which shows great potential in clinic.

We present a second near-infrared (NIR-II) self-checking molecule, LET-1052, for acidic tumor microenvironment (TME) turn-on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self-checking" strategy. In acidic TME, LET-1052 was protonated and turned on NIR-II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT-induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET-1052, resulting in the enhancement of NIR-I fluorescence for real-time evaluation of PTT efficacy. After PTT of tumor-bearing mice for different periods of NIR-II laser irradiation, NIR-I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine.

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. Graphical Abstract

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. Graphic abstract