Yuan Zhang

Lymphoma is a heterogeneous malignant proliferative disease of lymphocytes, with characteristics of liquid tumor and solid tumor. With the emergence of targeted drugs, monoclonal antibodies, bispecific antibodies, antibody-drug conjugates, and CAR-T therapy, the treatment landscape for lymphoma has been transformed. However, these therapies also possess limitations such as short plasma circulation time, low bioavailability, the development of drug resistance, and dose-dependent toxicity. With the advancement of nanotechnology, nanotech-based targeted delivery systems enable tumor-specific targeting and reduce off-target toxicity. Nano-immunotherapeutic systems, such as nanobody-based CAR-T therapy and mRNA-LNP nanovaccines, address limitations like drug resistance and relapse caused by antigen escape, inducing long-term anti-tumor immunity. Furthermore, smart designs responsive to the tumor microenvironment (TME) can significantly enhance drug accumulation and release efficiency at the lesion site. Innovative nanotech-based therapies are progressively transitioning from the laboratory to the clinic. By designing targeted nanocarriers, nano-immunotherapies, and TME-responsive intelligent nanotherapeutic platforms, targeted delivery of anti-lymphoma drugs can be achieved, enhancing efficacy and reducing toxicity. Simultaneously, these platforms can integrate multiple therapeutic modalities (such as chemodynamic therapy, immunomodulation, and gene silencing) to achieve synergistic and enhanced anti-lymphoma effects, offering new paradigms for lymphoma treatment.

IntroductionThe misfolding and aggregation of proteins are associated with various neurodegenerative diseases, such as Alzheimer's disease (AD). The small-molecule engineered antibodies, such as single-chain fragment variable (scFv) antibodies and nanobodies (Nbs), have gained attention in recent years due to their strong conformational specificity, ability to cross the blood-brain barrier (BBB), low immunogenicity, and enhanced proximity to active sites within aggregates.Areas coveredWe have reviewed recent advances in therapies involving scFvs and Nbs that efficiently and specifically target pathological protein aggregates. Relevant publications were searched for in MEDLINE, GOOGLE SCHOLAR, Elsevier ScienceDirect and Wiley Online Library.Expert opinionWe reviewed the recent and specific targeting of pathological protein aggregates by scFvs and Nbs. These engineered antibodies can inhibit the aggregation or promote the disassembly of misfolded proteins by recognizing antigenic epitopes or through conformational specificity. Additionally, we discuss strategies for improving the effective application of engineered antibodies in treating AD. These technological strategies will lay the foundation for the clinical application of small-molecule antibody drugs in developing effective treatments for neurological diseases. Through rational application strategies, small-molecule engineered antibodies are expected to have significant potential in targeted therapy for neurological disorders.

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated) system has proven to be a powerful tool for nucleic acid detection due to its inherent advantages of effective nucleic acid identification and editing capabilities, and is therefore known as the next-generation of molecular diagnostic technology. However, the detection technologies based on CRISPR/Cas systems require preamplification of target analytes; that is, target gene amplification steps through isothermal amplification or PCR before detection to increase target analyte concentrations. This creates a number of testing limitations, such as extended testing time and the need for more sophisticated testing instruments. To overcome the above limitations, various amplification-free assay strategies based on CRISPR/Cas systems have been explored as alternatives, which omit the preamplification step to increase the concentrations of the target analytes. Nanozymes play a pivotal role in enhancing the sensitivity of CRISPR-based detection, enabling visual and rapid CRISPR assays. The utilization of nanozyme exceptional enzyme-like catalytic activity holds great promise for signal amplification in both electrochemical and optical domains, encompassing strategies for electrochemical signal sensors and colorimetric signal sensors. Rather than relying on converting a single detection target analyte into multiple analytes, these methods focus on signal amplification, the main mechanism of which involves the ability to form a large number of reporter molecules or to improve the performance of the sensor. This exploitation of nanozymes for signal amplification results in the heightened sensitivity and accuracy of detection outcomes. In addition to the strategies that improve sensor performance through the application of nanozymes, additional methods are needed to achieve visual signal amplification strategies without preamplification processes. Herein, we review the strategies for improving CRISPR/Cas systems that do not require preamplification, providing a simple, intuitive and preamplification-free CRISPR/Cas system detection platform by improving in-system one-step amplification programs, or enhancing nanozyme-mediated signal amplification strategies.

Nanozymes are nanomaterials with catalytic properties similar to those of natural enzymes, and they have recently been collectively identified as a class of innovative artificial enzymes. Nanozymes are widely used in various fields, such as biomedicine, due to their high catalytic activity and stability. Nanozymes can trigger changes in reactive oxygen species (ROS) levels in cells and the activation of inflammasomes, leading to the programmed cell death (PCD), including the pyroptosis, ferroptosis, and autophagy, of tumor cells. In addition, some nanozymes consume glucose, starving cancer cells and thus accelerating tumor cell death. In addition, the electric charge of the structure and the catalytic activity of nanozymes are sensitive to external factors such as light and electric and magnetic fields. Therefore, nanozymes can be used with different therapeutic methods, such as chemodynamic therapy (CDT), photodynamic therapy (PDT) and sonodynamic therapy (SDT), to achieve highly efficient antitumor effects. Many cancer therapies induce tumor cell death via the pyroptosis, ferroptosis, and autophagy of tumor cells mediated by nanozymes. We review the mechanisms of pyroptosis, ferroptosis, and autophagy in tumor development, as well as the potential application of nanozymes to regulate pyroptosis, ferroptosis, and autophagy in tumor cells.

Nanozymes are a class of nanomaterials with enzyme-like catalytic activities. Due to their multiple catalytic activities, as well as their good stability, modifiable activity and other advantages over natural enzymes, they have a wide range of application prospects in sterilization, the treatment of inflammation, cancer, and neurological diseases, and other fields. In recent years, it has been found that various nanozymes have antioxidant activity, allowing them to simulate the endogenous antioxidant system and play an important role in cell protection. Therefore, nanozymes can be applied in the treatment of reactive oxygen species (ROS)-related neurological diseases. Another advantage of nanozymes is that they can be customized and modified in a variety of ways to increase their catalytic activity beyond that of classical enzymes. In addition, some nanozymes have unique properties, such as the ability to effectively penetrate the blood‒brain barrier (BBB) or to depolymerize or otherwise eliminate misfolded proteins, making them potentially useful therapeutic tools for the treatment of neurological diseases. Here, we review the catalytic mechanisms of antioxidant-like nanozymes, as well as the latest research progress and strategies for designing therapeutic nanozymes, aiming to promote the development of more effective nanozymes for the treatment of neurological diseases in the future.

Polyphenols are secondary metabolites of plants and play a potential role in the prevention and treatment of neurodegenerative diseases (NND) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) due to their unique physiological functions such as acting as antioxidants, being anti-inflammatory, being neuroprotective, and promoting intestinal health. Since dietary polyphenols exist in plant foods in the form of glycosylation or esterification or are combined with polymers, they need to undergo extensive metabolism through phase I and phase II biotransformations by various intestinal enzymes, as well as metabolism by the intestinal microbiota before they can be fully absorbed. Polyphenols improve intestinal microbiota disorders by influencing the structure and function of intestinal microbiota, inducing beneficial bacteria to produce a variety of metabolites such as short-chain fatty acids (SCFAs), promoting the secretion of hormones and neurotransmitters, and playing an important role in the prevention and treatment of NND by affecting the microbe–gut–brain axis. We review the ways in which some polyphenols can change the composition of the intestinal microbiota and their metabolites in AD or PD animal models to exert the role of slowing down the progression of NND, aiming to provide evidence for the role of polyphenols in slowing the progression of NND via the microbiota–gut–brain (MGB) axis.

The pathophysiological process of intracerebral hemorrhage (ICH) is very complex, involving various mechanisms such as apoptosis, oxidative stress and inflammation. As one of the key factors, the inflammatory response is responsible for the pathological process of acute brain injury and is associated with the prognosis of patients. Abnormal or dysregulated inflammatory responses after ICH can aggravate cell damage in the injured brain tissue. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex distributed in the cytosol, which can be triggered by multiple signals. The NLRP3 inflammasome is activated after ICH, thus promoting neuroinflammation and aggravating brain edema. In addition, there is evidence that the gut microbiota is crucial in the activation of the NLRP3 inflammasome. The gut microbiota plays a key role in a variety of CNS disorders. Changes in the diversity and species of the gut microbiota affect neuroinflammation through the activation of the NLRP3 inflammasome and the release of inflammatory cytokines. In turn, the gut microbiota composition can be influenced by the activation of the NLRP3 inflammasome. Thereby, the regulation of the microbe–gut–brain axis via the NLRP3 inflammasome may serve as a novel idea for protecting against secondary brain injury (SBI) in ICH patients. Here, we review the recent evidence on the functions of the NLRP3 inflammasome and the gut microbiota in ICH, as well as their interactions, during the pathological process of ICH.