Oral Hydrogel Microbeads-Mediated In Situ Synthesis of Selenoproteins for Regulating Intestinal Immunity and Microbiota.

Selenoprotein plays a crucial role in immune cells and inflammatory regulation. However, as a protein drug that is easily denatured or degraded in the acidic environment of the stomach, efficient oral delivery of selenoprotein is a great challenge. Herein, we innovated an oral hydrogel microbeads-based biochemical strategy that can in situ synthesize selenoproteins, therefore bypassing the necessity and harsh conditions for oral protein delivery while effectively generating selenoproteins for therapeutic applications. The hydrogel microbeads were synthesized by coating hyaluronic acid-modified selenium nanoparticles with a protective shell of calcium alginate (SA) hydrogel. We tested this strategy in mice with inflammatory bowel disease (IBD), one of the most representative diseases related to intestinal immunity and microbiota. Our results revealed that hydrogel microbeads-mediated in situ synthesis of selenoproteins could prominently reduce proinflammatory cytokines secretion and mediate immune cells (e.g., reduce neutrophils and monocytes and increase immune regulatory T cells) to effectively relieve colitis-associated symptoms. This strategy was also able to regulate gut microbiota composition (increase probiotics abundance and suppress detrimental communities) to maintain intestinal homeostasis. Considering intestinal immunity and microbiota widely associated with cancers, infections, inflammations, etc., this in situ selenoprotein synthesis strategy might also be possibly applied to broadly tackle various diseases.

In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer treatment.

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.

Minimally invasive nanomedicine: nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging.

Traditional treatments such as chemotherapy and surgery usually cause severe side effects and excruciating pain. The emergence of nanomedicines and minimally invasive therapies (MITs) has brought hope to patients with malignant diseases. Especially, minimally invasive nanomedicines (MINs), which combine the advantages of nanomedicines and MITs, can effectively target pathological cells/tissues/organs to improve the bioavailability of drugs, minimize side effects and achieve painless treatment with a small incision or no incision, thereby acquiring good therapeutic effects. In this review, we provide a comprehensive review of the research status and challenges of MINs, which generally refers to the medical applications of nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging. Additionally, we also discuss their combined application in various fields including cancers, cardiovascular diseases, tissue engineering, neuro-functional diseases, and infectious diseases. The prospects, and potential bench-to-bedside translation of MINs are also presented in this review. We expect that this review can inspire the broad interest for a wide range of readers working in the fields of interdisciplinary subjects including (but not limited to) chemistry, nanomedicine, bioengineering, nanotechnology, materials science, pharmacology, and biomedicine.

Selective CO2 Reduction to Ethylene Mediated by Adaptive Small-molecule Engineering of Copper-based Electrocatalysts.

Electrochemical CO2 reduction reaction (CO2 RR) over Cu catalysts exhibits enormous potential for efficiently converting CO2 to ethylene (C2 H4 ). However, achieving high C2 H4 selectivity remains a considerable challenge due to the propensity of Cu catalysts to undergo structural reconstruction during CO2 RR. Herein, we report an in situ molecule modification strategy that involves tannic acid (TA) molecules adaptive regulating the reconstruction of a Cu-based material to a pathway that facilitates CO2 reduction to C2 H4 products. An excellent Faraday efficiency (FE) of 63.6 % on C2 H4 with a current density of 497.2 mA cm-2 in flow cell was achieved, about 6.5 times higher than the pristine Cu catalyst which mainly produce CH4 . The in situ X-ray absorption spectroscopy and Raman studies reveal that the hydroxyl group in TA stabilizes Cuδ+ during the CO2 RR. Furthermore, theoretical calculations demonstrate that the Cuδ+ /Cu0 interfaces lower the activation energy barrier for *CO dimerization, and hydroxyl species stabilize the *COH intermediate via hydrogen bonding, thereby promoting C2 H4 production. Such molecule engineering modulated electronic structure provides a promising strategy to achieve highly selective CO2 reduction to value-added chemicals.

NIR-II Responsive Hydrogel as an Angiogenesis Inhibition Agent for Tumor Microenvironment Reprogramming.

Regulation of angiogenesis is a great challenge for effective anticancer therapy. Generally, anti-angiogenic therapies are focused on inhibition of inducers involved in pro-angiogenic communication pathways. Despite the great potential of anti-angiogenic therapy, engineering efficient angiogenesis inhibition agents (AIAs) is still a formidable challenge, since most anti-angiogenic therapies are limited due to the cancer recurrence via compensatory expression of different angiogenic mediators. Herein, we present a new strategy of near-infrared-II (NIR-II) responsive hydrogel AIAs, constructed by incorporation of nitric oxide (NO) precursor (BNN6) and 2D WO2.9 nanosheets within hydrogel (WB@hydrogel). Because of the defect/2D engineering, the bandgap of the WO2.9 nanosheets narrows, which extends the absorption to the NIR-II region. It offers a favorable NIR-II controlled manner for NO generation through irradiation time and light intensity. The continuous supply of NO can activate the expression of wild-type p53 protein and further reverse the transcriptional expression of pro- and anti-angiogenic factors of the tumor microenvironment (TME), subsequently alternating pro-angiogenic TME to anti-angiogenic TME. In the murine tumor model, this method achieved high tumor growth inhibition (TGI) rate and excellent anti-recurrence efficiency.

Stanene-Based Nanosheets for ß-Elemene Delivery and Ultrasound-Mediated Combination Cancer Therapy.

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.

Emerging two-dimensional monoelemental materials (Xenes) for biomedical applications.

The emergence of novel two-dimensional (2D) monoelemental materials (Xenes) has shown remarkable potential for their applications in different fields of technology, as well as addressing new discoveries in fundamental science. Xenes (e.g., borophene, silicene, germanene, stanene, phosphorene, arsenene, antimonene, bismuthene, and tellurene) are of particular interest because they are the most chemically tractable materials for synthetic exploration. Owing to their excellent physical, chemical, electronic and optical properties, Xenes have been regarded as promising agents for biosensors, bioimaging, therapeutic delivery, and theranostics, as well as in several other new bio-applications. In this tutorial review, we summarize their general properties including the classification of Xenes according to their bulk properties. The synthetic and modification methods of Xenes are also presented. Furthermore, the representative Xene nanoplatforms for various biomedical applications are highlighted. Finally, research progress, challenges, and perspectives for the future development of Xenes in biomedicines are discussed.

Emerging Two-Dimensional Nanomaterials for Cancer Therapy.

Two-dimensional (2D) nanomaterials have drawn tremendous attention due to their unique physicochemical properties and promising applications in the fields of electronics, energy storage, and catalysis. Recently, the biomedicine community has gradually started to recognize the great potential of these nanostructured materials for biomedical applications - in particular those related to cancer therapy. In this review, we provide a brief overview of a few representative 2D nanomaterials, discuss their preparation strategies and physicochemical properties, and highlight their applications in cancer nanomedicine. We expect that this review will shed some light on the new opportunities associated with 2D nanomaterials for biomedical research.

Artificial Enzyme Catalyzed Cascade Reactions: Antitumor Immunotherapy Reinforced by NIR-II Light.

Current cancer therapy is seriously challenged by tumor metastasis and recurrence. One promising solution to these problems is to build antitumor immunity. However, immunotherapeutic efficacy is highly impeded by the immunosuppressive state of the tumors. Here a new strategy is presented, catalytic immunotherapy based on artificial enzymes. Cu2-x Te nanoparticles exhibit tunable enzyme-mimicking activity (including glutathione oxidase and peroxidase) under near-infrared-II (NIR-II) light. The cascade reactions catalyzed by the Cu2-x Te artificial enzyme gradually elevates intratumor oxidative stress to induce immunogenic cell death. Meanwhile, the continuously generated oxidative stress by the Cu2-x Te artificial enzyme reverses the immunosuppressive tumor microenvironment, and boosts antitumor immune responses to eradicate both primary and distant metastatic tumors. Moreover, immunological memory effect is successfully acquired after treatment with the Cu2-x Te artificial enzyme to suppress tumor relapse.

2D Monoelemental Germanene Quantum Dots: Synthesis as Robust Photothermal Agents for Photonic Cancer Nanomedicine.

As a new family member of the emerging two-dimensional (2D) monoelemental materials (Xenes), germanene has shown promising advantages over the prototypical 2D Xenes, such as black phosphorus (BP) and graphene. However, efficient manufacture of novel germanene nanostructures is still a challenge. Herein, a simple top-down approach for the liquid-exfoliation of ultra-small germanene quantum dots (GeQDs) is presented. The prepared GeQDs possess an average lateral size of about 4.5 nm and thickness of about 2.2 nm. The functionalized GeQDs were demonstrated to be robust photothermal agents (PTAs) with outstanding photothermal conversion efficacy (higher than those of graphene and BPQDs), superior stability, and excellent biocompatibility. As a proof-of-principle, 2D GeQDs-based PTAs were used in fluorescence/photoacoustic/photothermal-imaging-guided hyperpyrexia ablation of tumors. This work could expand the application of 2D germanene to the field of photonic cancer nanomedicine.

Oral Nanomedicine: Challenges and Opportunities.

Compared to injection administration, oral administration is free of discomfort, wound infection, and complications and has a higher compliance rate for patients with diverse diseases. However, oral administration reduces the bioavailability of medicines, especially biologics (e.g., peptides, proteins, and antibodies), due to harsh gastrointestinal biological barriers. In this context, the development and prosperity of nanotechnology have helped improve the bioactivity and oral availability of oral medicines. On this basis, first, the biological barriers to oral administration are discussed, and then oral nanomedicine based on organic and inorganic nanomaterials and their biomedical applications in diverse diseases are reviewed. Finally, the challenges and potential opportunities in the future development of oral nanomedicine, which may provide a vital reference for the eventual clinical transformation and standardized production of oral nanomedicine, are put forward.

Resolvin D1 delivery to lesional macrophages using antioxidative black phosphorus nanosheets for atherosclerosis treatment.

The buildup of plaques in atherosclerosis leads to cardiovascular events, with chronic unresolved inflammation and overproduction of reactive oxygen species (ROS) being major drivers of plaque progression. Nanotherapeutics that can resolve inflammation and scavenge ROS have the potential to treat atherosclerosis. Here we demonstrate the potential of black phosphorus nanosheets (BPNSs) as a therapeutic agent for the treatment of atherosclerosis. BPNSs can effectively scavenge a broad spectrum of ROS and suppress atherosclerosis-associated pro-inflammatory cytokine production in lesional macrophages. We also demonstrate ROS-responsive, targeted-peptide-modified BPNS-based carriers for the delivery of resolvin D1 (an inflammation-resolving lipid mediator) to lesional macrophages, which further boosts the anti-atherosclerotic efficacy. The targeted nanotherapeutics not only reduce plaque areas but also substantially improve plaque stability in high-fat-diet-fed apolipoprotein E-deficient mice. This study presents a therapeutic strategy against atherosclerosis, and highlights the potential of BPNS-based therapeutics to treat other inflammatory diseases.

Harnessing inhaled nanoparticles to overcome the pulmonary barrier for respiratory disease therapy.

The lack of effective treatments for pulmonary diseases presents a significant global health burden, primarily due to the challenges posed by the pulmonary barrier that hinders drug delivery to the lungs. Inhaled nanomedicines, with their capacity for localized and precise drug delivery to specific pulmonary pathologies through the respiratory route, hold tremendous promise as a solution to these challenges. Nevertheless, the realization of efficient and safe pulmonary drug delivery remains fraught with multifaceted challenges. This review summarizes the delivery barriers associated with major pulmonary diseases, the physicochemical properties and drug formulations affecting these barriers, and emphasizes the design advantages and functional integration of nanomedicine in overcoming pulmonary barriers for efficient and safe local drug delivery. The review also deliberates on established nanocarriers and explores drug formulation strategies rooted in these nanocarriers, thereby furnishing essential guidance for the rational design and implementation of pulmonary nanotherapeutics. Finally, this review cast a forward-looking perspective, contemplating the clinical prospects and challenges inherent in the application of inhaled nanomedicines for respiratory diseases.

Nanomedicine for T-Cell Mediated Immunotherapy.

T-cell immunotherapy offers outstanding advantages in the treatment of various diseases, and with the selection of appropriate targets, efficient disease treatment can be achieved. T-cell immunotherapy has made great progress, but clinical results show that only a small proportion of patients can benefit from T-cell immunotherapy. The extensive mechanistic work outlines a blueprint for using T cells as a new option for immunotherapy, but also presents new challenges, including the balance between different fractions of T cells, the inherent T-cell suppression patterns in the disease microenvironment, the acquired loss of targets, and the decline of T-cell viability. The diversity, flexibility, and intelligence of nanomedicines give them great potential for enhancing T-cell immunotherapy. Here, how T-cell immunotherapy strategies can be adapted with different nanomaterials to enhance therapeutic efficacy is discussed. For two different pathological states, immunosuppression and immune activation, recent advances in nanomedicines for T-cell immunotherapy in diseases such as cancers, rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis, and diabetes are summarized. With a focus on T-cell immunotherapy, this review highlights the outstanding advantages of nanomedicines in disease treatment, and helps advance one's understanding of the use of nanotechnology to enhance T-cell immunotherapy.

Bioinspired Mild Photothermal Effect-Reinforced Multifunctional Fiber Scaffolds Promote Bone Regeneration.

Bone fractures are often companied with poor bone healing and high rates of infection. Early recruitment of mesenchymal stem cells (MSCs) is critical for initiating efficient bone repair, and mild thermal stimulation can accelerate the recovery of chronic diseases. Here, a bioinspired, staged photothermal effect-reinforced multifunctional scaffold was fabricated for bone repair. Uniaxially aligned electrospun polycaprolactone nanofibers were doped with black phosphorus nanosheets (BP NSs) to endow the scaffold with excellent near-infrared (NIR) responsive capability. Apt19S was then decorated on the surface of the scaffold to selectively recruit MSCs toward the injured site. Afterward, microparticles of phase change materials loaded with antibacterial drugs were also deposited on the surface of the scaffold, which could undergo a solid-to-liquid phase transition above 39 °C, triggering the release of payload to eliminate bacteria and prevent infection. Under NIR irradiation, photothermal-mediated up-regulation of heat shock proteins and accelerated biodegradation of BP NSs could promote the osteogenic differentiation of MSCs and biomineralization. Overall, this strategy shows the ability of bacteria elimination, MSCs recruitment, and bone regeneration promotion with the assistance of photothermal effect in vitro and in vivo, which emphasizes the design of a bioinspired scaffold and its potential for a mild photothermal effect in bone tissue engineering.

Transcriptome analysis unveils the mechanisms of lipid metabolism response to grayanotoxin I stress in Spodoptera litura.

Background: Spodoptera litura (tobacco caterpillar, S. litura) is a pest of great economic importance due to being a polyphagous and world-distributed agricultural pest. However, agricultural practices involving chemical pesticides have caused resistance, resurgence, and residue problems, highlighting the need for new, environmentally friendly methods to control the spread of S. litura. Aim: This study aimed to investigate the gut poisoning of grayanotoxin I, an active compound found in Pieris japonica, on S. litura, and to explore the underlying mechanisms of these effects. Methods: S. litura was cultivated in a laboratory setting, and their survival rate, growth and development, and pupation time were recorded after grayanotoxin I treatment. RNA-Seq was utilized to screen for differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to determine the functions of these DEGs. ELISA was employed to analyze the levels of lipase, 3-hydroxyacyl-CoA dehydrogenase (HOAD), and acetyl-CoA carboxylase (ACC). Hematoxylin and Eosin (H & E) staining was used to detect the development of the fat body. Results: Grayanotoxin I treatment significantly suppressed the survival rate, growth and development, and pupation of S. litura. RNA-Seq analysis revealed 285 DEGs after grayanotoxin I exposure, with over 16 genes related to lipid metabolism. These 285 DEGs were enriched in the categories of cuticle development, larvae longevity, fat digestion and absorption. Grayanotoxin I treatment also inhibited the levels of FFA, lipase, and HOAD in the hemolymph of S. litura. Conclusion: The results of this study demonstrated that grayanotoxin I inhibited the growth and development of S. litura. The mechanisms might, at least partly, be related to the interference of lipid synthesis, lipolysis, and fat body development. These findings provide valuable insights into a new, environmentally-friendly plant-derived insecticide, grayanotoxin I, to control the spread of S. litura.

Effects of Litsea cubeba essential oil on growth performance, blood antioxidation, immune function, apparent digestibility of nutrients, and fecal microflora of pigs.

The purpose of this experiment was to investigate the effects of Litsea cubeba essential oil (LCO) on the growth performance, blood antioxidation, immune function, apparent digestibility of nutrients, and fecal microflora in fattening pigs. A total of 120 pigs were randomly assigned to five groups, with six replicate pens per treatment and four pigs per pen, and they were fed basal diet, chlortetracycline (CTC), and low-, medium-, and high-concentration LCO. The results of the study showed that compared with the control treatment and CTC addition treatment of the basic diet, the catalase level in the serum of the pigs treated with 500 mg/kg LCO in the diet of finishing pigs was significantly increased (p < 0.05). The apparent digestibility of crude protein, crude ash, and calcium in pigs with different levels of LCO was significantly increased compared with the control treatments fed the basal diet (p < 0.05). In addition, compared with the control treatment fed the basal diet and the treatment with CTC, the apparent digestibility of ether extract in pigs treated with medium-dose LCO was significantly increased (p < 0.05), and the apparent digestibility of pigs was significantly increased after the addition of low-dose LCO (p < 0.05). Among the genera, the percentage abundance of SMB53 (p < 0.05) was decreased in the feces of the CTC group when compared to that in the medium-LCO group. At the same time, the relative abundance of L7A_E11 was markedly decreased in the feces of the control and medium- and high-concentration LCO group than that in the CTC group (p < 0.05). In conclusion, adding the level of 250 mg/kg LCO in the diet of pig could improve the growth performance and blood physiological and biochemical indicators of pigs, improve the antioxidant level of body and the efficiency of digestion and absorption of nutrients, and show the potential to replace CTC.

2D materials-based nanomedicine: From discovery to applications.

Due to their unique physicochemical characteristics, 2D materials have attracted more and more attention in the biomedicine field. Currently, 2D materials-based nanomedicines have been extensively applied in various diseases including cancer, bacterial infection, tissue engineering, biological protection, neurodegenerative diseases, and cardiovascular disease. Depending on their various characteristics, these 2D nanomedicines exert their therapeutic effect in different ways, showing great clinical application prospects. Herein, we focus on the various biomedical applications of 2D materials-based nanomedicine. The structures and characteristics of several typical 2D nanomaterials with different configurations and their corresponding biomedical applications are first introduced. Then, the potential of 2D nanomedicines on therapeutic and imaging and their biological functionalization are discussed. Furthermore, the therapeutic potentials of 2D nanomedicines in various diseases are also comprehensively summarized. At last, the challenges and perspectives for the advancement of 2D nanomedicines in clinical transformation are outlooks.

Carbon nanomaterials for drug delivery and tissue engineering.

Carbon nanomaterials are some of the state-of-the-art materials used in drug-delivery and tissue-engineering research. Compared with traditional materials, carbon nanomaterials have the advantages of large specific surface areas and unique properties and are more suitable for use in drug delivery and tissue engineering after modification. Their characteristics, such as high drug loading and tissue loading, good biocompatibility, good targeting and long duration of action, indicate their great development potential for biomedical applications. In this paper, the synthesis and application of carbon dots (CDs), carbon nanotubes (CNTs) and graphene in drug delivery and tissue engineering are reviewed in detail. In this review, we discuss the current research focus and existing problems of carbon nanomaterials in order to provide a reference for the safe and effective application of carbon nanomaterials in drug delivery and tissue engineering.

Emerging vaccine nanotechnology: From defense against infection to sniping cancer.

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.