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Oxidative stress is associated with many acute and chronic inflammatory diseases, yet limited treatment is currently available clinically. The development of enzyme-mimicking nanomaterials (nanozymes) with good reactive oxygen species (ROS) scavenging ability and biocompatibility is a promising way for the treatment of ROS-related inflammation. Herein we report a simple and efficient one-step development of ultrasmall Cu 5.4 O nanoparticles (Cu 5.4 O USNPs) with multiple enzyme-mimicking and broad-spectrum ROS scavenging ability for the treatment of ROS-related diseases. Cu 5.4 O USNPs simultaneously possessing catalase-, superoxide dismutase-, and glutathione peroxidase-mimicking enzyme properties exhibit cytoprotective effects against ROS-mediated damage at extremely low dosage and significantly improve treatment outcomes in acute kidney injury, acute liver injury and wound healing. Meanwhile, the ultrasmall size of Cu 5.4 O USNPs enables rapid renal clearance of the nanomaterial, guaranteeing the biocompatibility. The protective effect and good biocompatibility of Cu 5.4 O USNPs will facilitate clinical treatment of ROS-related diseases and enable the development of next-generation nanozymes. Oxidative stress is involved in several diseases and is a target for intervention. Here, the authors report on the synthesis of ultrasmall copper-based nanozymes as reactive oxygen species scavengers and demonstrate improved treatment outcomes in acute liver and kidney injury and wound healing in vivo.

Peptide self-assemblies with multiple nanostructures have great potentials in functional biomaterials, and yet the tedious and costly covalent peptide modification and the lack of facile controllability on self-assembly morphology retard the peptide-related exploration. Here we report a simple approach to fabricate a supramolecular peptide that shows programmable self-assembly with multiple morphologies and application in photodynamic therapy. Pillar[5]arene-based host−guest recognition is used to construct a supramolecular peptide, which simplify the peptide modification and promote the controllability of the self-assembly behavior. Due to the ERGDS sequences on the exterior surfaces and hydrophobic cores of self-assemblies, the nanoparticles formed from the supramolecular peptide are suitable vehicles to encapsulate a photosensitizer for photodynamic therapy. In vitro and in vivo studies demonstrate that the inherent targeting capability and supramolecular strategy greatly boost its photodynamic therapeutic efficiency. This supramolecular peptide holds promising potentials in precise cancer therapy and perspectives for the peptide modification. Despite its application in functional materials, covalent peptide modification and controlling peptide self-assembly remains challenging. Here the authors report a programmable supramolecular peptide by pillararene-based noncovalent interactions with multiple self-assembly morphologies and application in PDT.

The development of smart theranostic systems with favourable biocompatibility, high loading efficiency, excellent circulation stability, potent anti-tumour activity, and multimodal diagnostic functionalities is of importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain the major obstacles for clinical translation. Herein we prepare theranostic shell-crosslinked nanoparticles (SCNPs) using a β -cyclodextrin-based polyrotaxane (PDI-PCL- b -PEG-RGD⊃ β -CD-NH 2 ) to avoid premature drug leakage and achieve precisely controllable release, enhancing the maximum tolerated dose of the supramolecular nanomedicines. cRGDfK and perylene diimide are chosen as the stoppers of PDI-PCL- b -PEG-RGD⊃ β -CD-NH 2 , endowing the resultant SCNPs with excellent integrin targeting ability, photothermal effect, and photoacoustic capability. In vivo anti-tumour studies demonstrate that drug-loaded SCNPs completely eliminate the subcutaneous tumours without recurrence after a single-dose injection combining chemotherapy and photothermal therapy. These supramolecular nanomedicines also exhibit excellent anti-tumour performance against orthotopic breast cancer and prevent lung metastasis with negligible systemic toxicity. Multifunctional nanomedicine platforms are highly promising for anticancer therapy. Here, the authors design polyrotaxane-based theranostic nanoparticles that combine targeted drug delivery with photothermal behaviour to exhibit potent anti-tumour effects in vivo.

Uncontrolled haemorrhage is a leading cause of trauma-related fatalities, highlighting the critical need for rapid and effective haemostasis. Current haemostatic materials encounter limitations such as slow clotting and weak mechanical strength, while most of bioadhesives compromise their adhesion performance to wet tissues for biocompatibility and degradability. In this study, a molecular self-assembly strategy is proposed, developing a biocompatible and biodegradable protein-based patch with excellent adhesion performance. This strategy utilizes fibrinogen modified with hydrophobic groups to induce self-assembly into a hydrogel, which is converted into a dry patch. The protein patch enhances adhesion performance on the wet tissue through a dry cross-linking method and robust intra/inter-molecular interactions. This patch demonstrates excellent haemostatic efficacy in  both porcine oozing wound and porcine severe acute haemorrhage. It maintains biological functionality, and ensures sustained wound sealing while gradually degrading in vivo, making it a promising candidate for clinical tissue sealing applications. Bioadhesives can be used as potential haemostatic agents. Here, the authors report on a dry crosslinking protein patch, using a molecular self-assembly strategy, to create a biocompatible and biodegradable haemostatic material, demonstrating application in acute haemorrhage models.

Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen ( 1 O 2 ) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis -(PEt 3 ) 2 Pt(OTf) 2 as the building block to improve the 1 O 2 QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics. It is challenging to design photosensitizers (PS) with high quantum yields generating singlet oxygen due to severe aggregation between the hydrophobic PSs. Here they develop organoplatinum(II) metallatocage-based PS to overcome these challenges and show excellent antitumor effect.

The incorporation of new modalities into chemotherapy greatly enhances the anticancer efficacy combining the merits of each treatment, showing promising potentials in clinical translations. Herein, a hybrid nanomedicine (Au/FeMOF@CPT NPs) is fabricated using metal–organic framework (MOF) nanoparticles and gold nanoparticles (Au NPs) as building blocks for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT), and the hybridization by Au NPs greatly improves the stability of the nanomedicine in a physiological environment. Triggered by the high concentration of phosphate inside the cancer cells, Au/FeMOF@CPT NPs effectively collapse after internalization, resulting in the complete drug release and activation of the cascade catalytic reactions. The intracellular glucose can be oxidized by Au NPs to produce hydrogen dioxide, which is further utilized as chemical fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy. Benefitting from the enhanced permeability and retention effect and sophisticated fabrications, the blood circulation time and tumor accumulation of Au/FeMOF@CPT NPs are significantly increased. In vivo results demonstrate that the combination of chemotherapy and chemodynamic therapy effectively suppresses the tumor growth, meantime the systemic toxicity of this nanomedicine is greatly avoided. A hybrid nanomedicine (Au/FeMOF@CPT NPs) consisting of metal–organic framework nanoparticles (MOF NPs) and Au NPs is developed for cancer chemo/chemodynamic therapy. MOF NPs are used as vehicles to encapsulate camptothecin (CPT). H2O2 from the oxidation of intracellular glucose by Au NPs is further utilized as fuel for the Fenton reaction, thus realizing the synergistic anticancer efficacy.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) are prevalent critical illnesses with a high mortality rate among patients in intensive care units. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of ALI/ARDS and represent a promising therapeutic target. However, the clinical application of deoxyribonuclease I (DNase I), the only drug currently available to clear NETs, is limited due to the lack of precise and efficient delivery strategies. Therefore, targeted delivery of DNase I to the inflamed lung remains a critical issue to be addressed. Herein, a novel biomimetic DNase I delivery system is developed (DCNV) that employs genetically and bioorthogonally engineered cellular nanovesicles for pulmonary NETs clearance. The CXC motif chemokine receptor 2 overexpressed cellular nanovesicles can mimic the inflammatory chemotaxis of neutrophils in ALI/ARDS, leading to enhanced lung accumulation. Furthermore, DNase I immobilized through bioorthogonal chemistry exhibits remarkable enzymatic activity in NETs degradation, thus restraining inflammation and safeguarding lung tissue in the lipopolysaccharide‐induced ALI murine model. Collectively, the findings present a groundbreaking proof‐of‐concept in the utilization of biomimetic cellular nanovesicles to deliver DNase I for treating ALI/ARDS. This innovative strategy may usher in a new era in the development of pharmacological interventions for various inflammation‐related diseases.

Oxidative stress and inflammation are at the root of a multitude of diseases. Treatment of these conditions is often necessary but current standard therapies to fight excessive reactive oxygen species (ROS) and inflammation are often ineffective or complicated by substantial safety concerns. Nanozymes are emerging nanomaterials with intrinsic enzyme‐like properties that hold great promise for effective cancer treatment, bacterial elimination, and anti‐inflammatory/anti‐oxidant therapy. While there is rapid progress in tailoring their catalytic activities as evidenced by the recent integration of single‐atom catalysts (SACs) to create next‐generation nanozymes with superior activity, selectivity, and stability, a better understanding and tuning of their safety profile is imperative for successful clinical translation. This review outlines the current applied safety assessment approaches and provides a comprehensive summary of the safety knowledge of therapeutic nanozymes. Overall, nanozymes so far show good in vitro and in vivo biocompatibility despite considerable differences in their composition and enzymatic activities. However, current safety investigations mostly cover a limited set of basic toxicological endpoints, which do not allow for a thorough and deep assessment. Ultimately, remaining research gaps that should be carefully addressed in future studies are highlighted, to optimize the safety profile of therapeutic nanozymes early in their pre‐clinical development. Nanozymes spark attention as emerging nanotherapeutics due to their impressive medicinal potential across a wide range of diseases. Nevertheless, beyond therapeutic efficacy, nanomedicines must undergo rigorous safety assessment to ensure successful clinical translation. This comprehensive review outlines the current safety landscape of therapeutic nanozymes and highlights future research directions aimed at enhancing the current safety assessment.

With the development of personalized medical demands for precise diagnosis, rational management and effective cancer treatment, supramolecular theranostic systems have received widespread attention due to their reversibly switchable structures, sensitive response to biological stimuli and integration ability for multiple capabilities in a single platform with a programmable fashion. Cyclodextrins (CDs), benefiting from their excellent characteristics, such as non-toxicity, easy modification, unique host–guest properties, good biocompatibility, etc., as building blocks, serve as an all-purpose strategy for the fabrication of a supramolecular cancer theranostics nanodevice that is capable of biosafety, controllability, functionality and programmability. This review focuses on the supramolecular systems of CD-bioimaging probes, CD-drugs, CD-genes, CD-proteins, CD-photosensitizers and CD-photothermal agents as well as multicomponent cooperation systems with regards to building a nanodevice with functions of diagnosis and (or) therapeutics of cancer treatment. By introducing several state-of-the-art examples, emphasis will be placed on the design of various functional modules, the supramolecular interaction strategies under the fantastic topological structures and the hidden “bridge” between their structures and therapeutic efficacy, aiming for further comprehension of the important role of a cyclodextrin-based nanoplatform in advancing supramolecular cancer theranostics.

Catalytic therapy utilizing special substances (e.g., hydrogen peroxide and glucose) in tumor sites has attracted wide interest to achieve tumor‐specific therapy or improve the efficacy of other treatments. Benefiting from the selectivity and high activity of catalytic chemistry, efficient cancer therapy is available with negligible side effects. Numerous works, which are focused on further augmenting catalytic therapy with cascade strategies, have been reported with biocompatible nanomaterials composed of natural enzymes and/or nanozymes. Herein, we summarized catalytic reactions and nanomaterials in cascade strategy‐involved cancer therapy. With rapid advances in chemistry and nanomaterials, developing more selective and efficient cascade catalytic strategies will continue to be promising and challenging for cancer therapy.