Nanozyme-based therapeutics: bridging catalysis and nanomedicine

A Magnetocatalytic Propelled Cobalt–Platinum@Graphene Navigator for Enhanced Tumor Penetration and Theranostics

Microscale acoustic streaming for biomedical and bioanalytical applications

Nanozymes, a distinctive class of nanomaterials endowed with enzyme-like activity and kinetics akin to enzyme-catalysed reactions, present several advantages over natural enzymes, including cost-effectiveness, heightened stability, and adjustable activity. However, the conventional trial-and-error methodology for developing novel nanozymes encounters growing challenges as research progresses. The advent of artificial intelligence (AI), particularly machine learning (ML), has ushered in innovative design approaches for researchers in this domain. This review delves into the burgeoning role of ML in nanozyme research, elucidating the advancements achieved through ML applications. The review explores successful instances of ML in nanozyme design and implementation, providing a comprehensive overview of the evolving landscape. A roadmap for ML-assisted nanozyme research is outlined, offering a universal guideline for research in this field. In the end, the review concludes with an analysis of challenges encountered and anticipates future directions for ML in nanozyme research. The synthesis of knowledge in this review aims to foster a cross-disciplinary study, propelling the revolutionary field forward.

Biology-Oriented Design Strategies of AIE Theranostic Probes

With a rapid advancement of nanotechnology and the close integration of disciplines, research on nanozymes (nanomaterials with enzyme-like activities), is becoming an expeditiously developing field. In recent years, platinum group element (PGE)-based (Pt, Pd, Ru, Rh, Ir, and Os) nanozymes developed successively, have not only promoted the research of nanozymes but also expanded the biomedical applications of nanomaterials. Generally speaking, PGE-based nanozymes process high catalytic efficiency, specific surface area, stability, and other physical/chemical properties, which benefit for their applications in biosensing, biological medicine, biomedical imaging, and environmental protection. This paper will introduce the research progress of PGE-based nanozymes including their synthesis, characterization, enzyme-like activities, stability, biocompatibility, toxicity, and applications for biological detection and clinical relevance. Our emphasis is put on unfolding the roles of PGE-based nanozymes in biomedical applications and how they overcome the limitations. Last but not least, trends and future perspectives of PGE-based nanozymes in biomedical applications are also provided.

Nanoporous metals obtained by dealloying have attracted significant attention for their unusual catalytic properties, and as model materials for fundamental studies of structure-property relationships in a variety of research areas. There has been a recent surge in the use of these metals for biomedical and bioanalytical applications, where many exciting opportunities exist. The goal of this article is to provide a review of recent progress in using nanoporous metals for biological applications, including as biosensors for detecting biomarkers of disease and multifunctional neural interfaces for monitoring and modulating the activity of neural tissue. The article emphasizes the unique properties of nanoporous gold and concludes by discussing its utility in addressing important challenges in biomedical devices.

Nanocarriers are gaining significant importance in the modern era of drug delivery. Nanofiber technology is one of the prime paradigms in nanotechnology for various biomedical and theranostic applications. Nanofibers obtained after successful electrospinning subjected to surface functionalized for drug delivery, biomedical, tissue engineering, biosensing, cell imaging and wound dressing application. Surface functionalization entirely changes physicochemical and biological properties of nanofibers. In physicochemical properties, wettability, melting point, glass transition temperature, and initial decomposition temperature significantly change offer several advantageous for nanofibers. Similarly, biological properties include cell adhesion, biocompatibility, and proliferation, also changes by functionalization of nanofibers. Various natural and synthetic materials polymers, metals, carbon materials, functional groups, proteins, and peptides, are currently used for surface modification of nanofibers. Various research studies across the globe demonstrated the usefulness of surface functionalized nanofibers in tissue engineering, wound healing, skin cancers, melanoma, and disease diagnosis. The delivery of drug through surface functionalized nanofibers results in improved permeation and bioavailability of drug which is important for better targeting of disease and therapeutic efficacy. This review provides a comprehensive insight about various techniques of surface functionalization of nanofibers along with its biomedical applications, toxicity assessment and global patent scenario.

Glucose oxidase (GOD) is an oxidoreductase that catalyzes the aerobic oxidation of glucose into hydrogen peroxide (H2O2) and gluconic acid, which has been widely used in industrial raw materials production, biosensors and cancer treatment. However, natural GOD bears intrinsic disadvantages, such as poor stability and a complex purification process, which undoubtedly restricts its biomedical applications. Fortunately, several artificial nanomaterials have been recently discovered with a GOD-like activity and their catalytic efficiency toward glucose oxidation can be finely optimized for diverse biomedical applications in biosensing and disease treatments. In view of the notable progress of GOD-mimicking nanozymes, this review systematically summarizes the representative GOD-mimicking nanomaterials for the first time and depicts their proposed catalytic mechanisms. We then introduce the efficient modulation strategy to improve the catalytic activity of existing GOD-mimicking nanomaterials. Finally, the potential biomedical applications in glucose detection, DNA bioanalysis and cancer treatment are highlighted. We believe that the development of nanomaterials with a GOD-like activity will expand the application range of GOD-based systems and lead to new opportunities of GOD-mimicking nanomaterials for various biomedical applications.

Nanodiamonds for bioapplications–specific targeting strategies

Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents

Nanozymes are nanomaterials with enzyme-like activities and have become a research hotspot in tumor therapy due to their exceptional properties. However, biological application of nanozymes remains a methodology and safety issue. More systematic and rational design of nanozymes is needed for better tumor treatment. In this Perspective, we focus on the key questions that need to be addressed in nanozyme research, including the catalytic mechanism elucidation and the construction of structure-activity relationship, and introduce several promising rational design methods as well as prospect the future development of nanozymes. This Perspective aims to help researchers clarify the rational design of nanozymes in tumor therapy, offering a comprehensive guide in this emerging field.

Information plays a critical role in complex biological systems. Complex systems like immune systems and ant colonies co-ordinate heterogeneous components in a decentralized fashion. How do these distributed decentralized systems function? One key component is how these complex systems efficiently process information. These complex systems have an architecture for integrating and processing information coming in from various sources and points to the value of information in the functioning of different complex biological systems. This article proposes a role for information processing in questions around the origin of life and suggests how computational simulations may yield insights into questions related to the origin of life. Such a computational model of the origin of life would unify thermodynamics with information processing and we would gain an appreciation of why proteins and nucleotides evolved as the substrate of computation and information processing in living systems that we see on Earth. Answers to questions like these may give us insights into non-carbon based forms of life that we could search for outside Earth. We hypothesize that carbon-based life forms are only one amongst a continuum of systems in the universe. Investigations into the role of computational substrates that allow information processing is important and could yield insights into: 1) novel non-carbon based computational substrates that may have life-like properties, and 2) how life may have actually originated from non-life on Earth. Life may exist as a continuum between non-life and life and we may have to revise our notion of life and how common it is in the universe. Looking at life or phenomenon through the lens of information theory may yield a broader view of life.

Synthetic biology is an emerging field blending approaches and concepts derived from classic engineering disciplines with modern biological approaches. Concepts of modularity and orthogonality, i.e. the transfer of simple building blocks between unrelated chassis (host organisms), are guiding principles for the design and construction of artificial biological systems, which in their ultimate implementation can be artificial organisms. Synthetic biology is not only leading the way towards the engineering of useful organisms that serve human purposes, it is also a new way of approaching basic scientific questions to understand complex biological systems. The classic reductionist methodology by which scientists have dissected complex systems to understand their properties through understanding the functionality of isolated components, finds its counterpart in synthetic biology. If we can build complex biological processes, systems, and ultimately organisms from simple, fully understood functional modules using a set of defined rules, we must fully understand the system. At first this approach may sound almost naïve as with near certainty scientists will encounter spectacular 'failures' on the way to building complex biological systems. Undoubtedly, the result of synthetic biology efforts will be more than the sum of the individual components giving rise to complex systems with novel emergent properties, many of which are unexpected or even undesired. However, the process of learning from those 'failures' often through predictive modeling and simulation studies in parallel to the actual assembly and testing of artificial biological systems, will lead to novel insights into the function of complex biological systems in general. Plant and algal cells are complex with their extra organelle, the plastid, and are highly sophisticated in their metabolism enabling them to convert light, CO2 and minerals into the building blocks of cells, produce all oxygen in the atmosphere, thousands of specialized chemicals including drugs, and energy-rich compounds that fuel life on earth. While engineers have been dabbling for many years in the redesign of bacterial and yeast chassis with novel properties, the application of synthetic biology to photosynthetic organisms is just beginning. Therefore, it seems timely to provide an overview of the state of the art of 'Synthetic Biology for Basic and Applied Plant Research' in this special issue of The Plant Journal. Next Generation Sequencing has given us a nearly unlimited number of genomic blueprints for photosynthetic bacteria, algae and plants and this provides the raw material for synthetic biology. Tools for recombining of genes and introducing them into an increasing number of photosynthetic chassis including organelles such as chloroplasts, are available and no longer an impediment to the application of synthetic biology to plants. One revolutionary technique, the introduction of the CRISPR/CAS system for genome editing is now being applied to edit not only the plant genome, but also the transcriptome and epigenome as discussed by Puchta (2016). Bacterial microcompartments, first discovered as carboxysomes in cyanobacteria, provide an important platform for the engineering of synthetic modules. They can encapsulate enzymes, concentrate substrates, and help in the avoidance of toxic products as Gonzalez-Esquer et al. (2016) describe. Cyanobacteria address one key problem that all photosynthetic organisms encounter, the natural inefficiency of the carbon-fixing enzyme RubBisCO, by encapsulating this enzyme in carboxysomes, which increases the local concentration of CO2 around the enzyme. Plants do not have a carboxysome-based carbon concentration mechanism to overcome the limitation of photosynthesis through RubBisCO's inefficiency. The solution could be to introduce this bacterial microcompartment into chloroplasts of crop plants and synthetic biology efforts towards this aim are well under way as described by Hanson et al. (2016). A subset of plants has evolved their own way of overcoming this problem by prefixing carbon using a more efficient enzyme than RubBisCO. This carbon concentration mechanism requires the compartmentalization of different sets of enzymes in different cells of the leaf, and this overall approach is referred to as C4-syndrome of C4 plants, because the CO2 is first fixed into a four-carbon compound rather than the three-carbon compound produced first by RuBisCO in C3 plants. Some of the important crop plants that feed the world are C4 plants, such as maize, but many are not, including wheat and rice. The solution is to engineer C4 photosynthesis in a C3 chassis and as Schuler et al. (2016) describe, efforts are well underway by applying synthetic biology. Introduction of orthogonal biosynthetic pathways into photosynthetic organelles and bacteria to enhance their synthetic repertoires requires a deep knowledge of the regulation of photosynthesis, as the balance of ATP/and NADPH and the nature of the carbon sink are critical for the efficiency of photosynthesis. Nielson and coworkers describe how optimization of carbon flux and reductant are critical elements in engineering cyanobacteria and chloroplasts to sustainably produce novel chemicals (Nielsen et al., 2015). Plants are capable of making a seemingly unlimited number of specialized compounds to defend themselves against pathogens or herbivores and many of these compounds have been used by humans for thousands of years, e.g. as drugs. One particular compound class, the terpenoids, provides an example of the amazing natural combinatorial chemistry that plants are capable of. Applying synthetic biology principles of modularity and orthogonality, plant engineers are now capable of recombining different modules of terpenoid biosynthesis from different sources into new chassis to engineer plants that produce new-to-nature compounds as Arendt et al. (2016) describe. Another spectacular success in recombining modules of genes derived from different plants, algae, and fungi into a new chassis, the industrial crop Camelina, is the production of oils with a near natural composition of healthy oils found in fish as summarized by Haslam et al. (2016). With this accomplishment, important sustainability and human health questions can be addressed. These include improving the sustainability of the aquaculture industry for the production of fish rich in omega-3 oils with well-known health benefits when part of the human diet. Another example of addressing pressing problems for humankind is the generation of sustainable feed-stocks for energy production, independent of fossil fuels. For this reason, many scientists are currently pursuing the engineering of dedicated biofuel crops through the application of synthetic biology principles as summarized by Shih et al. (2016). Plant signaling pathways are highly interconnected and redundant, and hence often hard to dissect using the classical reductionistic approaches. Synthetic Biology offers a new way to explore individual signaling pathways by reassembling them bottom up from modules in non-interfering backgrounds of new chassis. Braguy and Zurbriggen (2016) describe this approach in detail. Ultimately, understanding how signaling pathways feed into programmable plant genetic circuits will be essential for the engineering of plants to be more efficient or to produce novel compounds. Medford and Prasad (2016) explain how genetic parts such as promoters and other regulatory elements can be tested and their assembly into genetic circuits simulated. The list of examples and approaches described in this special issue of The Plant Journal is comprehensive. Our intention is that this special issue will explain key principles and areas of plant synthetic biology to guide the reader and future contributors of The Plant Journal in embracing these approaches for both fundamental and applied plant science. Other areas of interest not covered here include synthetic consortia, the synthetic interaction of photosynthetic and heterotrophic organisms beyond naturally occurring symbioses. As we learn to understand how the microbiome affects plant growth, synthetic biology approaches may be key in learning more about these complex interactions, a topic that certainly falls with in the scope of The Plant Journal. With the expansion of the current field of plant synthetic biology, The Plant Journal welcomes the submission of basic research papers applying synthetic biology to further our understanding of the full biological complexity of photosynthetic organisms and their complex biotic and abiotic interaction with the environment.

Cytochrome P450 1A (CYP1A), one of the most important phase I drug-metabolizing enzymes in humans, plays a crucial role in the metabolic activation of procarcinogenic compounds to their ultimate carcinogens. Herein, we reported the development of a ratiometric two-photon fluorescent probe NCMN that allowed for selective and sensitive detection of CYP1A for the first time. The probe was designed on the basis of substrate preference of CYP1A and its high capacity for O-dealkylation, while 1,8-naphthalimide was selected as fluorophore because of its two-photon absorption properties. To achieve a highly selective probe for CYP1A, a series of 1,8-naphthalimide derivatives were synthesized and used to explore the potential structure-selectivity relationship, by using a panel of human CYP isoforms for selectivity screening. After screening and optimization, NCMN displayed the best combination of selectivity, sensitivity and ratiometric fluorescence response following CYP1A-catalyzed O-demetylation. Furthermore, the probe can be used to real-time monitor the enzyme activity of CYP1A in complex biological systems, and it has the potential for rapid screening of CYP1A modulators using tissue preparation as enzyme sources. NCMN has also been successfully used for two-photon imaging of intracellular CYP1A in living cells and tissues, and showed high ratiometric imaging resolution and deep-tissue imaging depth. In summary, a two-photon excited ratiometric fluorescent probe NCMN has been developed and well-characterized for sensitive and selective detection of CYP1A, which holds great promise for bioimaging of endogenous CYP1A in living cells and for further investigation on CYP1A associated biological functions in complex biological systems.

Iron oxide nanoparticles (IONPs) are frequently used in biomedical applications, yet their toxic potential is still a major concern. While most studies of biosafety focus on cellular responses after exposure to nanomaterials, little is reported to analyze reactions on the surface of nanoparticles as a source of cytotoxicity. Here we report that different intracellular microenvironment in which IONPs are located leads to contradictive outcomes in their abilities to produce free radicals. We first verified pH-dependent peroxidase-like and catalase-like activities of IONPs and investigated how they interact with hydrogen peroxide (H(2)O(2)) within cells. Results showed that IONPs had a concentration-dependent cytotoxicity on human glioma U251 cells, and they could enhance H(2)O(2)-induced cell damage dramatically. By conducting electron spin resonance spectroscopy experiments, we showed that both Fe(3)O(4) and γ-Fe(2)O(3) nanoparticles could catalyze H(2)O(2) to produce hydroxyl radicals in acidic lysosome mimic conditions, with relative potency Fe(3)O(4) > γ-Fe(2)O(3), which was consistent with their peroxidase-like activities. However, no hydroxyl radicals were observed in neutral cytosol mimic conditions with both nanoparticles. Instead, they decomposed H(2)O(2) into H(2)O and O(2) directly in this condition through catalase-like activities. Transmission electron micrographs revealed that IONPs located in lysosomes in cells, the acidic environment of which may contribute to hydroxyl radical production. This is the first study regarding cytotoxicity based on their enzyme-like activities. Since H(2)O(2) is continuously produced in cells, our data indicate that lysosome-escaped strategy for IONP delivery would be an efficient way to diminish long-term toxic potential.