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Bacillus subtilis, as a biocontrol bacterium, possess a variety of biological functions and the capacity to control plant pathogens. Iturin A is a biosurfactant with broad-spectrum antifungal activity produced by fermentation of B. subtilis. In this study, the dynamic parameters of solid-state fermentation (SSF) and submerged fermentation (SMF) of Bacillus velezensis ND were compared, and a method for producing iturin A with a yield of 12.46 g/kg utilizing SSF was proposed. It has significant advantages over SMF and has the highest yield of all previously reported studies. B. velezensis ND also contains protease activity, cellulase activity, iron-carrying activity, the ability to synthesis 3-indoleacetic acid (IAA), fixation nitrogen, and degrade phosphorus. In cotton pot experiments, it can effectively increase cotton growth and minimize Verticillium wilt. This strain's superior fermentation efficiency, biological function, and biocontrol ability are sufficient to demonstrate its promise for the development and use of biocontrol agents.

The field of two-dimensional (2D) nanomaterial-based cancer immunotherapy combines research from multiple subdisciplines of material science, nano-chemistry, in particular nano-biological interactions, immunology, and medicinal chemistry. Most importantly, the “biological identity” of nanomaterials governed by bio-molecular corona in terms of bimolecular types, relative abundance, and conformation at the nanomaterial surface is now believed to influence blood circulation time, bio-distribution, immune response, cellular uptake, and intracellular trafficking. A better understanding of nano-bio interactions can improve utilization of 2D nano-architectures for cancer immunotherapy and immunotheranostics, allowing them to be adapted or modified to treat other immune dysregulation syndromes including autoimmune diseases or inflammation, infection, tissue regeneration, and transplantation. The manuscript reviews the biological interactions and immunotherapeutic applications of 2D nanomaterials, including understanding their interactions with biological molecules of the immune system, summarizes and prospects the applications of 2D nanomaterials in cancer immunotherapy., Graphical abstract The two-dimensional nanomaterials would affect and could modulate immune system via specific design, which endows them great potential in cancer immunotherapy.Image 1

Summary Oral delivery of insulin is of great convenience in treating diabetes but is still subject to the harsh gastrointestinal tract. Herein, we developed an intelligent oral insulin platform based on glucose-responsive polymeric nanoparticles (NPs), which possess the following advantages: (1) protect the integrity and bioavailability of loaded insulin against gastrointestinal tract, (2) overcome the intestinal epithelial barriers via neonatal Fc receptor-mediated transport, and (3) on-demand release of insulin dependent solely on blood glucose levels to avoid hyperglycemia and hypoglycemia caused by unsafe doses of insulin. Notably, our oral NPs extended the therapeutic effect to up to 16 h in type 1 diabetic mice. To our knowledge, this is the longest effective time among such types of oral insulin platforms reported to date and may reduce the frequency of insulin administration to once daily. This platform might be useful for the oral delivery of biologics in treating diabetes and related complications.

The local electron density of an atom is one key factor that determines its chemical properties. Regulating electron density can promote the atom's reactivity and so reduce the reaction activation energy, which is highly desired in many chemical applications. Herein, we report an intra-crystalline electron lever strategy, which can regulate the electron density of reaction centre atoms via manipulating ambient lattice states, for Fenton activity improvement. Typically, with the assistance of ultrasound, the Mn4+ -O-Fe3+ bond in BiFe0.97 Mn0.03 O3 perovskite nanocrystals can drive valence electrons and free electrons to accumulate on Fe atoms by a polarization electric field originated from the designed lattice strain. The increase of electron density significantly improves the catalytic activity of Fe, decreasing the activation energy of BiFe0.97 Mn0.03 O3 -mediated Fenton reaction by 52.55 %, and increasing the . OH yield by 9.21-fold. This study provides a new way to understand the sono-Fenton chemistry, and the increased . OH production enables a highly effective chemodynamic therapy.

Since the first connection between Fenton chemistry and biomedicine, numerous studies have been presented in this field. Comprehensive presentation of the guidance from Fenton chemistry and a summary of its representative applications in cancer therapy would help us understand and promote the further development of this field. This comprehensive review first supplies basic information regarding Fenton chemistry, including Fenton reactions and Fenton-like reactions. Subsequently, the current progress of Fenton chemistry is discussed, with some corresponding representative examples presented. Furthermore, the current strategies for further optimizing the performance of chemodynamic therapy guided by Fenton chemistry are highlighted. Most importantly, future perspectives on the combination of biomedicine with Fenton chemistry or a wider range of catalytic chemistry approaches are presented. We hope that this review will attract positive attention in the chemistry, materials science, and biomedicine fields and further tighten their connections.

Pnictogens (the non-metal phosphorus, metalloids arsenic and antimony, and metal bismuth) possess diverse chemical characteristics that support the formation of extended molecular structures. As witnessed by the centuries-old (and ongoing) clinical utilities, pnictogen-based compounds have secured their places in history as "magic bullet" therapeutic drugs in medicinal contexts. Moreover, with the development of recent metalloproteomics and bio-coordination chemistry, the pnictogen-based drugs functionally binding to proteins/enzymes in biological systems have been underlaid for "drug repurposing" with promising opportunities. Furthermore, advances in the modern materials science and nonotechnology have stimulated a revolution in other newly discovered forms of pnictogens-phosphorene, arsenene, antimonene, and bismuthine (layered pnictogens). Based on their favorable optoelectronic properties, layered pnictogens have shown dramatic superiority as emerging photonic nanomedicines for the treatment of various diseases. This tutorial review outlines the history and mechanism of action of ancient pnictogen-based drugs (e.g., arsenical compounds in traditional Chinese medicine) and their repurposing into modern therapeutics. Then, the revolutionary use of emerging layered pnictogens as photonic nanomedicines, alongside assessments of their in vivo biosafety, is discussed. Finally, the challenges to further development of pnictogens are set forth and insights for further exploration of their appealing properties are offered. This tutorial review may also provide some deep insights into the fields of integrated traditional Chinese and Western medicines from the perspective of materials science and nanotechnology.

Diabetes mellitus is a lifelong metabolic disease that requires frequent subcutaneous injections of insulin. However, this method of administration can be associated with patient discomfort and local tissue infection. Oral delivery of insulin has been pursued as a more convenient method for diabetes treatment, given its likely superior patient compliance and convenience as well as cost-effectiveness. However, various biological barriers hinder the clinical translation of oral insulin. The rapid development of nanotechnology over the last decade offers great promise in improving the bioavailability of oral insulin. This Minireview provides an overview of biological barriers to oral insulin delivery, summarizes significant technological advances, and outlines future perspectives in oral insulin formulations as well as their hypoglycaemic effects.

Summary Germanene (Ge) is a newly discovered two-dimensional (2D) monoelemental material whose biomedical applications remain largely unexplored. Here, we provide the proof-of-principle evidence of a 2D Ge-based strategy for surgical adjuvant treatment. The exfoliated Ge nanosheets (NSs) exhibited high drug-loading capacity, multiresponsive (pH- and near-infrared [NIR]-sensitive) drug-release behavior, NIR-triggered deep tumor penetration, good biocompatibility, and excellent multimodal imaging-guided treatment. When combined with hydrogel (composed of clinically approved agarose and chitosan), the developed drug-loaded Ge@hydrogel was coated on the postoperative wound surface after tumor removal. Followed by NIR irradiation, the generated local hyperthermia and NIR-triggered drug release achieved immediate residual tumor-eliminating and bacteria-killing effects, while the hydrogel served as a therapeutic reservoir for long-lasting antitumor and bactericidal effects. In summary, this is the first application of 2D Ge-based surgical adjuvant treatment, potentially marking a jumping-off point for future studies on biomedical applications of Ge.

In recent years, there have been significant innovations in the development of nanoparticle-based vaccines and vaccine delivery systems. For the purposes of both design and evaluation, these nanovaccines are imaged using the wealth of understanding established around medical imaging of nanomaterials. An important insight to the advancement of the field of nanovaccines can be given by an analysis of the design rationale of an imaging platform, as well as the significance of the information provided by imaging. Nanovaccine imaging strategies can be categorized by the imaging modality leveraged, but it is also worth understanding the superiority or convenience of a given modality over others in a given context of a particular nanovaccine. The most important imaging modalities in this endeavor are optical imaging including near-infrared fluorescence imaging (NIRF), emission tomography methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) with or without computed tomography (CT) or magnetic resonance (MR), the emerging magnetic particle imaging (MPI), and finally, multimodal applications of imaging which include molecular imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. One finds that each of these modalities has strengths and weaknesses, but optical and PET imaging tend, in this context, to be currently the most accessible, convenient, and informative modalities. Nevertheless, an important principle is that there is not a one-size-fits-all solution, and that the specific nanovaccine in question must be compatible with a particular imaging modality. This article is categorized under: Nanotechnology Approaches to BiologyNanoscale Systems in Biology Therapeutic Approaches and Drug DiscoveryNanomedicine for Oncologic Disease Therapeutic Approaches and Drug DiscoveryNanomedicine for Infectious Disease.

The great success achieved by the two highly-effective messenger RNA (mRNA) vaccines during the COVID-19 pandemic highlights the great potential of mRNA technology. Through the evolution of mRNA technology, chemistry has played an important role from mRNA modification to the synthesis of mRNA delivery platforms, which allows various applications of mRNA to be achieved both

Abnormal iron metabolism, mitochondrial dysfunction and the derived oxidative damage are the main pathogeneses of Friedrich's ataxia (FRDA), a single-gene inherited recessive neurodegenerative disease characterized by progressive cerebellar and sensory ataxia. This disease is caused by frataxin (FXN) mutation, which reduces FXN expression and impairs iron sulfur cluster biogenesis. To date, there is no effective therapy to treat this condition. Curcumin is proposed harboring excellent ability to resist oxidative stress through Nrf2 activation and its newly found ability to chelate iron. However, its limitation is its poor water solubility and permeability. Here, we synthesized slow-release nanoparticles (NPs) by loading curcumin (Cur) into silk fibroin (SF) to form NPs with an average size of 150 nm (Cur@SF NPs), which exhibited satisfactory therapeutic effects on the improvement of FRDA manifestation in lymphoblasts (1 μM) derived from FRDA patients and in YG8R mice (150 mg/kg/5 days). Cur@SF NPs not only removed iron from the heart and diminished oxidative stress in general but also potentiate iron-sulfur cluster biogenesis, which compensates FXN deficiency to improve the morphology and function of mitochondria. Cur@SF NPs showed a significant advantage in neuron and myocardial function, thereby improving FRDA mouse behavior scores. These data encourage us to propose that Cur@SF NPs are a promising therapeutic compound in the application of FRDA disease. Graphical Abstract

As an indispensable strategy for tumor treatment, surgery may cause two major challenges: tumor recurrence and wound infection. Here, a thermoelectric therapeutic strategy is provided as either an independent cancer therapy or surgical adjuvant treatment. Bi

RNA interference (RNAi) is a powerful approach in the treatment of various diseases including cancers. The clinical translation of small interfering RNA (siRNA)-based therapy requires safe and efficient delivery vehicles. Here, we report a siRNA nanogels (NG)-based delivery vehicle, which is driven directly by the intercalation between nucleic acid bis-intercalator and siRNA molecules. The intercalation-based siRNA NG exhibits good physiological stability and can enter cells efficiently via different endocytosis pathways. Furthermore, the siRNA NG can not only silence the target genes in vitro but also significantly inhibit the tumor growth in vivo. Therefore, this study provides an intercalation-based strategy for the development of a siRNA delivery platform for cancer therapy. To the best of our knowledge, this is the first report of the intercalation-driven siRNA NG.

Summary Phosphorus plays an indispensable role in energy metabolism, acid-base balance, and genetic substances transfer. As nanotechnology advances, plenty of phosphorus-based nanomaterials have been developed and widely used in the fields of biology and medicine. The size and structure of phosphorus-based nanomaterials give them unique physicochemical, optical, and biological properties, greatly increasing the variety of nanomedicine. The excellent properties further promote the applications of phosphorus-based nanomaterials in drug nanocarriers, tumor theranostics, biosensors, and bone formation. In this review, we first introduce the phosphorus science to unify current phosphorus-based nanomaterials and discuss their synthesis methods. Furthermore, the representative nanoplatforms utilizing the corresponding properties are highlighted. Finally, research development, potential challenges, and perspectives for further improvement of phosphorus-based nanomaterials in biomedicines are presented.

The aggregation of hydrophobic photosensitizers limits the therapeutic effect of photodynamic therapy (PDT). Improving the hydrophilicity of photosensitizers can reduce their aggregation for enhancing PDT. Herein, a nanosystem (TPFcNP) is developed by a hydrophobic photosensitizer 5,10,15,20-tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) containing multiple carbon-carbon double bonds and a ferrocene-containing amphiphilic block copolymer (PEG-b-PMAEFc), which catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH) in a tumor microenvironment by the Fenton reaction. The •OH could catalyze the addition reaction between the carbon-carbon double bonds of TMPP and overexpressed water-soluble glutathione (GSH) in tumor cells, which greatly improves the hydrophilicity of photosensitizers and reduces their aggregation. Experiments in vitro and in vivo have proved that this strategy significantly enhances the therapeutic efficacy of PDT. Catalyzing intracellular reactions in situ by making use of the tumor microenvironment will open up a new opportunity to solve the aggregation of materials in the tumor for cancer treatment.

Summary Calcium overload, characterized by an abnormal cytoplasm accumulation of free calcium ions (Ca2+), is a widely recognized cause of damage in numerous cell types and even of cell death. This undesirable destructive process can become a new tool applicable to cancer treatment. Herein, on the basis of the unique biological effect of Ca2+, we demonstrate a highly efficient strategy for tumor therapy by utilizing pH-sensitive sodium-hyaluronate-modified calcium peroxide nanoparticles (SH-CaO2 NPs). These NPs create an artificial calcium overloading stress in tumor cells, which is responsible for cell death. Notably, the killing effect is not limited to tumor types or hypoxic cells, and normal cells are more tolerant of the adverse influence of NPs than tumor cells. The Ca2+ enrichment also increases the likelihood of tumor calcification, which could contribute to in vivo tumor inhibition and facilitate medical imaging to monitor the treatment efficacy.

Highlights 2D Sn nanosheets (SnNSs) were prepared through the combination of cryogenic exfoliation and liquid-phase exfoliation.The functionalized 2D SnNSs have good stability, superior biocompatibility, high photothermal conversion efficiency, and multimode imaging capability. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00619-1., Stanene (Sn)-based materials have been extensively applied in industrial production and daily life, but their potential biomedical application remains largely unexplored, which is due to the absence of the appropriate and effective methods for fabricating Sn-based biomaterials. Herein, we explored a new approach combining cryogenic exfoliation and liquid-phase exfoliation to successfully manufacture two-dimensional (2D) Sn nanosheets (SnNSs). The obtained SnNSs exhibited a typical sheet-like structure with an average size of ~ 100 nm and a thickness of ~ 5.1 nm. After PEGylation, the resulting PEGylated SnNSs (SnNSs@PEG) exhibited good stability, superior biocompatibility, and excellent photothermal performance, which could serve as robust photothermal agents for multi-modal imaging (fluorescence/photoacoustic/photothermal imaging)-guided photothermal elimination of cancer. Furthermore, we also used first-principles density functional theory calculations to investigate the photothermal mechanism of SnNSs, revealing that the free electrons in upper and lower layers of SnNSs contribute to the conversion of the photo to thermal. This work not only introduces a new approach to fabricate 2D SnNSs but also establishes the SnNSs-based nanomedicines for photonic cancer theranostics. This new type of SnNSs with great potential in the field of nanomedicines may spur a wave of developing Sn-based biological materials to benefit biomedical applications. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00619-1.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non-invasiveness and high tissue-penetrating depth. However, developing biocompatible nanomaterial-based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid-phase exfoliation strategy to obtain a new type of two-dimensional (2D) stanene-based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano-sonosensitizers, allowing a more efficient US-triggered separation of electron (e- )-hole (h+ ) pairs for reactive oxygen species (ROS) generation. In addition, we discovered that such SnNSs could also serve as robust near-infrared (NIR)-mediated photothermal therapy (PTT) agents owing to their efficient photothermal conversion, and serve as nanocarriers for anticancer drug delivery owing to the inherent 2D layered structure. This study not only presents general nanoplatforms for SDT-enhanced combination cancer therapy, but also highlights the utility of 2D SnNSs to the field of nanomedicine.

To prevent the more severe spread of COVID-19 infections, sensitive, rapid, low-cost, and multiplexed detection is critical. Recently, Gao et al. reported a laser-engraved graphene-based wireless device to monitor multiple biomarkers from human biofluids, allowing for high-frequency self-testing of COVID-19 with high accuracy and low cost.

The treatment of diabetic ulcer (DU) remains a major clinical challenge due to the complex wound-healing milieu that features chronic wounds, impaired angiogenesis, persistent pain, bacterial infection, and exacerbated inflammation. A strategy that effectively targets all these issues has proven elusive. Herein, we use a smart black phosphorus (BP)-based gel with the characteristics of rapid formation and near-infrared light (NIR) responsiveness to address these problems. The in situ sprayed BP-based gel could act as 1) a temporary, biomimetic "skin" to temporarily shield the tissue from the external environment and accelerate chronic wound healing by promoting the proliferation of endothelial cells, vascularization, and angiogenesis and 2) a drug "reservoir" to store therapeutic BP and pain-relieving lidocaine hydrochloride (Lid). Within several minutes of NIR laser irradiation, the BP-based gel generates local heat to accelerate microcirculatory blood flow, mediate the release of loaded Lid for "on-demand" pain relief, eliminate bacteria, and reduce inflammation. Therefore, our study not only introduces a concept of in situ sprayed, NIR-responsive pain relief gel targeting the challenging wound-healing milieu in diabetes but also provides a proof-of-concept application of BP-based materials in DU treatment.

The ongoing SARS-CoV-2 pandemic highlights the importance of materials science in providing tools and technologies for antiviral research and treatment development. In this Review, we discuss previous efforts in materials science in developing imaging systems and microfluidic devices for the in-depth and real-time investigation of viral structures and transmission, as well as material platforms for the detection of viruses and the delivery of antiviral drugs and vaccines. We highlight the contribution of materials science to the manufacturing of personal protective equipment and to the design of simple, accurate and low-cost virus-detection devices. We then investigate future possibilities of materials science in antiviral research and treatment development, examining the role of materials in antiviral-drug design, including the importance of synthetic material platforms for organoids and organs-on-a-chip, in drug delivery and vaccination, and for the production of medical equipment. Materials-science-based technologies not only contribute to the ongoing SARS-CoV-2 research efforts but can also provide platforms and tools for the understanding, protection, detection and treatment of future viral diseases., Materials science provides tools and technologies for the protection against viral infections, as well as for the understanding, diagnosis, treatment and prevention of viral diseases. This Review discusses present and future directions in antiviral materials-science research, with a focus on COVID-19.

Clay-based nanomaterials, especially 2:1 aluminosilicates such as vermiculite, biotite, and illite, have demonstrated great potential in various fields. However, their characteristic sandwiched structures and the lack of effective methods to exfoliate two-dimensional (2D) functional core layers (FCLs) greatly limit their future applications. Herein, we present a universal wet-chemical exfoliation method based on alkali etching that can intelligently “capture” the ultrathin and biocompatible FCLs (MgO and Fe2O3) sandwiched between two identical tetrahedral layers (SiO2 and Al2O3) from vermiculite. Without the sandwich structures that shielded their active sites, the obtained FCL nanosheets (NSs) exhibit a tunable and appropriate electron band structure (with the bandgap decreased from 2.0 eV to 1.4 eV), a conductive band that increased from −0.4 eV to −0.6 eV, and excellent light response characteristics. The great properties of 2D FCL NSs endow them with exciting potential in diverse applications including energy, photocatalysis, and biomedical engineering. This study specifically highlights their application in cancer theranostics as an example, potentially serving as a prelude to future extensive studies of 2D FCL NSs., Clay-based nanomaterials are of wide interest but problems extracting the 2D functional core layers have limited potential applications. Here, the authors report on the wet exfoliation of vermiculite by alkali etching to obtain the core layers and explore the application of the materials in cancer theranostics.

The rapid development of nanotechnology results in the emergence of nanomedicines, but the effective delivery of drugs to tumor sites remains a great challenge. Prodrug-based cancer nanomedicines thus emerged due to their unique advantages, including high drug load efficiency, reduced side effects, efficient targeting, and real-time controllability. A distinctive characteristic of prodrug-based nanomedicines is that they need to be activated by a stimulus or multi-stimulus to produce an anti-tumor effect. A better understanding of various responsive approaches could allow researchers to perceive the mechanism of prodrug-based nanomedicines effectively and further optimize their design strategy. In this review, we highlight the stimuli-responsive pathway of prodrug-based nanomedicines and their anticancer applications. Furthermore, various types of prodrug-based nanomedicines, recent progress and prospects of stimuli-responsive prodrug-based nanomedicines and patient data in the clinical application are also summarized. Additionally, the current development and future challenges of prodrug-based nanomedicines are discussed. We expect that this review will be valuable for readers to gain a deeper understanding of the structure and development of prodrug-based cancer nanomedicines to design rational and effective drugs for clinical use.

The key bottleneck problem of chemodynamic therapy (CDT) is that the efficiency depends heavily on an acidic chemical environment. However, there is a sufficient blood supply on the surface of solid tumours, resulting in neutral-pH surface regions, strongly reducing the effectiveness of CDT. In this study, chelating complex ferrous-cysteine–phosphotungstate nanoparticles (FcPWNPs) are synthesized to serve as new CDT nanoagents that break through the limitation of a neutral pH, ensuring CDT efficiencies at both an acidic and neutral pH. The CDT efficiency is increased by introducing cysteine and phosphotungstate, which form an Fe chelating complex to inhibit the formation of inert Fe(OH)x, and accelerate electron transfer between ferric and ferrous ions, respectively. Due to this ferrous chelating strategy and associated electron transfer property, the FcPWNPs can destroy cancer cells from the neutral-pH tumour surface to the acidic interior, thus realizing a complete CDT cancer therapy.

The common existence of hypoxia in solid tumors has been heavily researched because it renders tumors more resistant to most standard therapeutic methods, such as radiotherapy (RT), chemotherapy, and photodynamic therapy (PDT), and is associated with a more malignant phenotype and poor survival in patients with tumors. The development of hypoxia modulation methods for advanced therapeutic activity is therefore of great interest but remains a considerable challenge. Since the significant development of nanotechnology and nanomedicine, functionalized nanomaterials can be exploited as adjuvant "drugs" for these oxygen-dependent standard therapies or as hypoxia initiators for advanced new therapies to solid tumors. In this Account, we summarize our recent studies on the design and synthesis of nanomaterials with a set of desired chemistry benefits achievable by modulating hypoxia, suggesting a valid therapeutic option for tumors. The investigated strategies can be categorized into three groups: The first strategy is based on countering hypoxia. Considering that O

X-ray-induced photodynamic therapy (X-PDT) has high depth of penetration and has considerable potential for applications in cancer therapy. Scintillators and heavy metals have been adopted to absorb X-rays and transmit the energy to photosensitizers. However, the low efficiency of converting X-rays to reactive oxygen species (ROS) presents a challenge for the use of X-PDT to cure cancer. In this study, a new method based on LiLuF4:Ce@SiO2@Ag3PO4@Pt(IV) nanoparticles (LAPNP) is presented that could be used to enhance the curative effects of X-PDT. To make full use of the fluorescence produced by nanoscintillators (LiLuF4:Ce), a cisplatin prodrug Pt(IV) was utilized as a sacrificial electron acceptor to increase the yield of hydroxyl radicals (·OH) by increasing the separation of electrons and holes in photosensitizers (Ag3PO4). Additionally, cisplatin is produced upon the acceptance of electrons by Pt(IV) and further enhances the damage caused by ·OH. Via two-step amplification, the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.