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Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion-induced pain, and pliable to infection. Here, a kind of ultra-hydrophobic haemostatic anti-adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic-modified cellulose nanocrystals (CNCs), achieving a water contact angle of ≈160° is developed. It is demonstrated that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood-restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs are combined. The produced ultra-hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peelable, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, this gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. This work presents promising applications in terms of prehospital first aid., (© 2024 Wiley‐VCH GmbH.)

Ulcerative colitis (UC) is a persistent inflammatory condition that specifically targets the colon and rectum. Existing therapies fail to adequately address the clinical requirements of people suffering from this ailment. Despite the acknowledged potential of nanomedicines in the field of anti-inflammatory treatment, their widespread use in clinical settings is impeded by their expensive nature and the uncertainty surrounding their safety profiles. This study illustrates that two naturally occurring phytochemicals, Costunolide (COS) and Glycyrrhizic acid (GA), form carrier-free, multifunctional spherical nanoparticles (NPs) through noncovalent interactions, such as π-π stacking and hydrogen bonding. The COS-GA NPs displayed a synergistic anti-inflammatory effect, providing much more evidently improved therapeutic benefits for dextran sodium sulfate (DSS)-induced UC mice due to more effective reduction in inflammation and oxidative stress than did equal dosages of COS or GA used alone. In addition, COS-GA NPs have biocompatibility and biosafety properties unique to them. This study will serve as affirmation of the potential of COS-GA NPs as innovative natural anti-inflammatory and antioxidant activities and also such agents as drug discovery in UC, leading possibly to better outcomes in people living with this disabling condition., (© 2024. The Author(s).)

Background: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated., Results: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-β/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-β/BMPR2/Smad pathway., Conclusions: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-β/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs., (© 2024. The Author(s).)

Nanoparticle vaccines displaying mosaic receptor-binding domains (RBDs) or spike (S) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other sarbecoviruses are used in preparedness against potential zoonotic outbreaks. Here, we describe a self-assembling nanoparticle using lumazine synthase (LuS) as the scaffold to display RBDs from different sarbecoviruses. Mosaic nanoparticles induce sarbecovirus cross-neutralizing antibodies comparable to a nanoparticle cocktail. We find mosaic nanoparticles elicit a B cell receptor repertoire using an immunodominant germline gene pair of IGHV14-3:IGKV14-111. Most of the tested IGHV14-3:IGKV14-111 monoclonal antibodies (mAbs) are broadly cross-reactive to clade 1a, 1b, and 3 sarbecoviruses. Using mAb competition and cryo-electron microscopy, we determine that a representative IGHV14-3:IGKV14-111 mAb, M2-7, binds to a conserved epitope on the RBD, largely overlapping with the pan-sarbecovirus mAb S2H97. This suggests mosaic nanoparticles expand B cell recognition of the common epitopes shared by different clades of sarbecoviruses. These results provide immunological insights into the cross-reactive responses elicited by mosaic nanoparticles against sarbecoviruses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Photodynamic therapy (PDT) is an effective approach for treating melanoma. However, the photosensitizers employed in PDT can accumulate in healthy tissues, potentially causing harm to normal cells and resulting in side effects such as heightened photosensitivity. To address this, an activatable photosensitizer (PSD) by linking PpIX with a fluorescence quencher using a disulfide bond is designed. PSD responded to endogenous GSH, showing high selectivity for A375 cells. To enhance PSD's bioavailability and anticancer efficacy, an enzyme-responsive nanoplatform based on a lonidamine-derived self-assembling peptide is developed. Initially, PSD and the peptide self-assembled into nanoparticles, displaying potent tumor targeting of PSD in vivo. Upon cell uptake, these nanoparticles specifically responded to elevated cathepsin B, causing nanoparticle disintegration and releasing PSD and lonidamine prodrug (LND-1). PSD is selectively activated by GSH for cancer-specific fluorescence imaging and precision PDT, while LND-1 targeted mitochondria, forming a fibrous lonidamine depot in situ and intensifying photosensitizer's cytotoxicity through ROS generation, mitochondrial dysfunction, and DNA damage. Notably, intravenous administration of LND-1-PEG@PSD with light irradiation significantly suppressed A375-xenografted mouse tumor growth, with minimal systemic toxicity. Together, the synergy of activatable photosensitizer and enzyme-responsive nanoplatform elevates PDT precision and diminishes side effects, showcasing significant potential in the realm of cancer nanomedicine., (© 2023 Wiley‐VCH GmbH.)

Background: Increasing attention is being paid to the environmental and health impacts of nanoplastics (NPs) pollution. Exposure to nanoplastics (NPs) with different charges and functional groups may have different adverse effects after ingestion by organisms, yet the potential ramifications on mammalian blood glucose levels, and the risk of diabetes remain unexplored., Results: Mice were exposed to PS-NPs/COOH/NH 2 at a dose of 5 mg/kg/day for nine weeks, either alone or in a T2DM model. The findings demonstrated that exposure to PS-NPs modified by different functional groups caused a notable rise in fasting blood glucose (FBG) levels, glucose intolerance, and insulin resistance in a mouse model of T2DM. Exposure to PS-NPs-NH 2 alone can also lead the above effects to a certain degree. PS-NPs exposure could induce glycogen accumulation and hepatocellular edema, as well as injury to the pancreas. Comparing the effect of different functional groups or charges on T2DM, the PS-NPs-NH 2 group exhibited the most significant FBG elevation, glycogen accumulation, and insulin resistance. The phosphorylation of AKT and FoxO1 was found to be inhibited by PS-NPs exposure. Treatment with SC79, the selective AKT activator was shown to effectively rescue this process and attenuate T2DM like lesions., Conclusions: Exposure to PS-NPs with different functional groups (charges) induced T2DM-like lesions. Amino-modified PS-NPs cause more serious T2DM-like lesions than pristine PS-NPs or carboxyl functionalized PS-NPs. The underlying mechanisms involved the inhibition of P-AKT/P-FoxO1. This study highlights the potential risk of NPs pollution on T2DM, and provides a new perspective for evaluating the impact of plastics aging., (© 2024. The Author(s).)

Along with the growing production and application of silica nanoparticles (SiNPs), increased human exposure and ensuing safety evaluation have progressively attracted concern. Accumulative data evidenced the hepatic injuries upon SiNPs inhalation. Still, the understanding of the hepatic outcomes resulting from SiNPs exposure, and underlying mechanisms are incompletely elucidated. Here, SiNPs of two sizes (60 nm and 300 nm) were applied to investigate their composition- and size-related impacts on livers of ApoE -/- mice via intratracheal instillation. Histopathological and biochemical analysis indicated SiNPs promoted inflammation, lipid deposition and fibrosis in the hepatic tissue, accompanied by increased ALT, AST, TC and TG. Oxidative stress was activated upon SiNPs stimuli, as evidenced by the increased hepatic ROS, MDA and declined GSH/GSSG. Of note, these alterations were more dramatic in SiNPs with a smaller size (SiNPs-60) but the same dosage. LC-MS/MS-based quantitative proteomics unveiled changes in mice liver protein profiles, and filtered out particle composition- or size-related molecules. Interestingly, altered lipid metabolism and oxidative damage served as two critical biological processes. In accordance with correlation analysis and liver disease-targeting prediction, a final of 10 differentially expressed proteins (DEPs) were selected as key potential targets attributable to composition- (4 molecules) and size-related (6 molecules) liver impairments upon SiNPs stimuli. Overall, our study provided strong laboratory evidence for a comprehensive understanding of the harmful biological effects of SiNPs, which was crucial for toxicological evaluation to ensure nanosafety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

After aging in the environment, some nanoplastics will carry different charges and functional groups, thereby altering their toxicological effects. To evaluate the potential impact of aging of nanoplastics on the mammalian reproductive system, we exposed C57BL/6 male mice to a dose of 5 mg/kg/d polystyrene nanoparticles (PS-NPs) with different functional groups (unmodified, carboxyl functionalized and amino functionalized) for 45 days for this study. The results suggest that PS-NPs with different functional groups triggered oxidative stress, a decreased in the testis index, disruption of the outer wall of the seminiferous tubules, reduction in the number of spermatogonia cells and sperm counts, and an increased in sperm malformations. We performed GO and KEGG enrichment analysis on the differentially expressed proteins, and found they were mainly enriched in protein transport, RNA splicing and mTOR signaling. We confirmed that the PI3K-AKT-mTOR pathway is over activated, which may lead to reduction of spermatogonia stem cells by over differentiation. Strikingly, PS-NPs with functional group modifications are more toxic than those of unmodified polystyrene, and that PS-NPs with positively charged amino modifications are the most toxic. This study provides a new understanding for correctly evaluating the toxicological effects of plastic aging, and of the mechanism responsible for the reproductive toxicity caused by nanoplastics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antibiotic detection is crucial and challenging because the widespread consumption of antibiotics has shown extensive harmful effects on food, environment and human health. Here, we propose highly water-soluble and biocompatible hyaluronic acid (HYA) functionalized upconversion nanoparticles (UCNPs) for ratiometric detection of multiple antibiotics. The ultraviolet upconversion luminescence (UCL) from UCNPs was significantly quenched by nitrofurazone (NFZ)/nitrofurantoin (NFT), and blue UCL was quenched by doxorubicin (DOX), while red UCL remained unchanged for internal reference. The UCNPs-HYA nanoprobes exhibit excellently sensitive and selective NFZ, NFT and DOX detection in linear range of 2.5-100 μM, 2.5-80 μM, and 2.5-200 μM with the LOD at 0.28 μM (55 μg/kg), 0.20 μM (48 μg/kg) and 0.17 μM (97 μg/kg), respectively. The nanoprobes achieved detecting real samples of NFZ in lake water, liquid milk and chicken meat with satisfactory results, and UCL bioimaging of DOX in HeLa cells. The UCNPs-HYA ratiometric nanoprobes are promising for food samples detection and potential biosensing in the cellular environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Synergistic therapy is expected to be a promising strategy for highly effective cancer treatment. However, the rational design of a simple and multifunctional nanoplatform still remains a grand challenge. Considering the nature of weak acidic, hypoxic, and H 2 O 2 abundant tumor microenvironment, we constructed an indocyanine green (ICG) modified platinum nanoclusters (Pt NCs) decorated gold nanobipyramids (Au NBPs) to form the multifunctional nanocomposites (Au NBPs@Pt NCs-ICG) for multimodal imaging mediated phototherapy and chemodynamic cancer therapy. The photosensitizer ICG was covalently linked to Au NBPs@Pt NCs by bridging molecules of SH-PEG-NH 2 for both photodynamic therapy (PDT) and fluorescence imaging. Besides, Au NBPs@Pt NCs-ICG nanocomposites exhibited catalase- and peroxidase-like activities to generate O 2 and ·OH, which relieved the tumor hypoxia and upregulated antitumoral ROS level. Moreover, the combination of Au NBPs and ICG endowed the Au NBPs@Pt NCs-ICG with super photothermal conversion for effective photothermal imaging and therapy. In addition, the Au NBPs@Pt NCs-ICG nanoplatform displayed excellent X-ray computed tomography (CT) imaging ability due to the presence of high-Z elements (Au and Pt). Overall, our results demonstrated that Au NBPs@Pt NCs-ICG nanoplatform exhibited a multimodal imaging guided synergistic PTT/PDT/CDT therapeutic manners and held great potential as an efficient treatment for breast cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The blood-brain barrier presents a key limitation to the administration of therapeutic molecules for the treatment of brain disease. While drugs administered orally or intravenously must cross this barrier to reach brain targets, the unique anatomical structure of the olfactory system provides a route to deliver drugs directly to the brain. Entering the brain via receptor, carrier, and adsorption-mediated transcytosis in the nasal olfactory and trigeminal regions has the potential to increase drug delivery. In this review, we introduce the physiological and anatomical structures of the nasal cavity, and summarize the possible modes of transport and the relevant receptors and carriers in the nose-to-brain pathway. Additionally, we provide examples of nanotherapeutics developed for intranasal drug delivery to the brain. Further development of nanoparticles that can be applied to intranasal delivery systems promises to improve drug efficacy and reduce drug resistance and adverse effects by increasing molecular access to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease., (© 2024 Wiley Periodicals LLC.)

Chemotherapeutic efficacy for pancreatic cancer is severely compromised by limited drug availability to tumor cells. Herein, we constructed a cancer cell membrane-fused liposome containing a siATG5-loaded calcium phosphate (CaP) core, termed CLip@siATG5. Through cancer cell membrane camouflage, the liposomes evaded immune clearance, actively infiltrated tumor tissues, and were preferentially taken up by homotypic tumor cells. Then, siATG5 escaped from the endosomes and was liberated in the cytoplasm, mainly benefiting from CaP dissolution-induced endosome rupture and liposome disassembly in acidic endosomes. The released siATG5 silenced autophagy protein 5 (ATG5) to inhibit autophagy, starving tumor cells. An alternative nutrient procurement pathway, macropinocytosis, was then upregulated in the cells, leading to increased uptake of the albumin-bound chemotherapeutic agent (nanoparticle albumin-bound paclitaxel (Nab-PTX)). Finally, in a murine pancreatic cancer model, CLip@siATG5 combined with Nab-PTX exerted superior efficacy to a twofold dose of Nab-PTX while avoiding its toxicity. Overall, we justified enhancing chemotherapeutic delivery by modulating the pancreatic cancer cell metabolism, which will enlighten the development of more effective chemotherapeutic adjuvants for pancreatic cancer in the future., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Nitrogen-doped graphene (C 2 N), a novel graphene-based materials, has been proposed as a potential alternative to graphene oxide (GO) in biomedical applications. However, due to the challenges in synthesizing C 2 N, reports in the biomedical field are currently rare. Here, we have modified the reported procedure and successfully synthesized C 2 N nanoparticles at 120°C, which we refer to as C 2 N-120. The toxicity and biocompatibility of GO and C 2 N-120 were evaluated using a mouse model injected with GO/C 2 N-120 via the tail vein, as well as cell models treated with GO/C 2 N-120. In vivo studies revealed that GO/C 2 N-120 showed similar distribution patterns after tail vein injection. The liver, spleen, and lung are the major nanoparticle uptake organs of GO and C 2 N-120. However, GO deposition in the major nanoparticle uptake organs was more significant than that of C 2 N-120. In addition, GO deposition caused structural abnormalities, increased apoptotic cells, and enhanced macrophage infiltration whereas C 2 N-120 exhibited fewer adverse effects. In vitro experiments were conducted using different cell lines treated with GO/C 2 N-120. Unlike GO which induced mitochondrial damage, oxidative stress, inflammatory response, autophagic flux blockage and cell apoptosis, C 2 N-120 showed lower cytotoxicity in cell models. Our data demonstrated that C 2 N-120 exhibits higher biocompatibility than GO, both in vivo and in vitro, suggesting its potential for biomedical application in the future., (© 2023 Wiley Periodicals LLC.)

Micro- and nanoplastics have recently been detected in human blood and placentas, indicating inevitable embryonic exposure to these particles. However, their influence on human embryogenesis and the underlying mechanisms are still unknown. In this study, the effects of polystyrene nanoplastics (PS-NPs) exposure on cardiac differentiation of human embryonic stem cells (hESCs) were evaluated. Uptake of PS-NPs not only caused cellular injury, but also regulated cardiac-related pathways as revealed by RNA-sequencing. Consequently, the efficiency of cardiomyocyte differentiation from hESCs was compromised, leading to immature of cardiomyocytes and smaller cardiac organoids with impaired contractility. Mechanistically, PS-NPs promoted mitochondrial oxidative stress, activated P38/Erk MAPK signaling pathway, blocked autophagy flux, and eventually reduced the pluripotency of hESCs. Consistently, in vivo exposure of PS-NPs from cleavage to gastrula period of zebrafish embryo led to reduced cardiac contraction and blood flow. Collectively, this study suggests that PS-NPs is a risk factor for fetal health, especially for heart development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Rapid endothelialization of cardiovascular materials can enhance the vascular remodeling performance. In this work, we developed a strategy for amyloid-like protein-assembly-mediated interfacial engineering to functionalize a biomimetic nanoparticle coating (BMC). Various groups (e.g., hydroxyl and carboxyl) on the BMC are responsible for chelating Zn 2+ ions at the stent interface, similar to the glutathione peroxidase-like enzymes found in vivo. This design could reproduce the release of therapeutic nitric oxide gas (NO) and an aligned microenvironment nearly identical with that of natural vessels. In a rabbit abdominal aorta model, BMC-coated stents promoted vascular healing through rapid endothelialization and the inhibition of intimal hyperplasia in the placement sites at 4, 12, and 24 weeks. Additionally, better anticoagulant activity and immunomodulation in the BMC stents were also confirmed, and vascular healing was mainly dependent on cell signaling through the cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) cascade. Overall, a metal-polypeptide-coated stent was developed on the basis of its detailed molecular mechanism of action in vascular remodeling.

Anti-tumor M1-like and pro-tumor M2-like tumor-associated macrophages (TAMs) coexist in tumor microenvironments (TME). The adverse effects of these M1/M2 subsets on tumors directly affect the current strategies to improve anti-tumor immune response. Therefore, it has attracted great attention to change the tumor immunosuppressive microenvironment by reprogramming TAMs. In this paper, we constructed biomimetic nanoparticles (HMMDN-Met@PM) targeting M2-like TAMs for macrophage re-polarization. In detail, the core of the biomimetic nanoparticles is metformin-loaded hollow mesoporous manganese dioxide nanoparticles (HMMDN-Met). Benefited from the hollow and porous structure of HMMDN, metformin, the regulator of M1/M2 adopted in this work, can be easily and widely loaded into HMMDN. Moreover, macrophage membranes were utilized for HMMDN-Met coating (HMMDN-Met@MM) to prevent the premature drug leakage and provide specific molecular recognition/TME targeting. In addition, M2 macrophage targeting peptide (M2pep) was modified on the surface of macrophage membrane to specifically deliver the drug to M2-like TAMs to promote the polarization of M2 to M1 macrophages. Through in vitro and in vivo studies, we found that the expression of surface markers and inflammatory factors CD206, Arg-1 and IL-10 of type M2 macrophages decreased, while the surface markers of type M1 macrophages and the expression of inflammatory factors CD80, TNF-α and iNOS increased, indicating the successful re-polarization of M2 macrophages and finally realizing the inhibition of tumor growth. At the same time, under the acidic and GSH conditions of tumor, HMMDN was decomposed into Mn 2+ , which is a contrast agent for magnetic resonance imaging, thus realizing the tracking of tumor. This work practices biomimetic nanosystem in targeted imaging and immunotherapy, paving the way for strategy designing for tumor inhibition., (© 2023. The Author(s).)

Low-temperature photothermal therapy (PTT) is a noninvasive method that harnesses the photothermal effect at low temperatures to selectively eliminate tumor cells, while safeguarding normal tissues, minimizing thermal damage, and enhancing treatment safety. First we evaluated the transcriptome of tumor cells at the gene level following low-temperature treatment and observed significant enrichment of genes involved in cell cycle and heat response-related signaling pathways. To address this challenge, we have developed an engineering multifunctional nanoplatform that offered an all-in-one strategy for efficient sensitization of low-temperature PTT. Specifically, we utilized MoS 2 nanoparticles as the photothermal core to generate low temperature (40-48 °C). The nanoplatform was coated with DPA to load CPT-11 and Fe 2+ and was further modified with PEG and iRGD to enhance tumor specificity (MoS 2 /Fe@CPT-11-PEG-iRGD). Laser- and acid-triggered release of CPT-11 can significantly increase intracellular H 2 O 2 content, cooperate with Fe 2+ ions to increase intracellular lipid ROS content, and activate ferroptosis. Furthermore, CPT-11 induced cell cycle arrest in the temperature-sensitive S-phase, and increased lipid ROS levels contributed to the degradation of HSPs protein expression. This synergistic approach could effectively induce tumor cell death by the sensitized low-temperature PTT and the combination of ferroptosis and chemotherapy. Our nanoplatform can also maximize tumor cell eradication and prolong the survival time of tumor-bearing mice in vivo. The multifunctional approach will provide more possibilities for clinical applications of low-temperature PTT and potential avenues for the development of multiple tumor treatments.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopamine (DA) neurons in the midbrain substantia nigra pars compacta (SNpc). While existing therapeutic strategies can alleviate PD symptoms, they cannot inhibit DA neuron loss. Herein, a tailor-made human serum albumin (HSA)-based selenium nanosystem (HSA/Se nanoparticles, HSA/Se NPs) to treat PD that can overcome the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) is described. HSA, a transporter for drug delivery, has superior biological characteristics that make it an ideal potential drug delivery substance. Findings reveal that HSA/Se NPs have lower toxicity and higher efficacy than other selenium species and the ability to overcome the IEB and BBB to enrich DA neurons, which then protect MN9D cells from MPP + -induced neurotoxicity and ameliorate both behavioral deficits and DA neuronal death in MPTP-model mice. Thus, a therapeutic drug delivery system composed of orally gavaged HSA/Se NPs for the treatment of PD is described.

In recent years, the popularity of dietary nanoparticles (NPs) in the food industry as additives has raised concerns because of the lack of knowledge about potential adverse health outcomes ensuing from the interactions of NPs with components of the food matrix and gastrointestinal system. In this study, we used a transwell culture system that consisted of human colorectal adenocarcinoma (Caco-2) cells in the apical insert and Laboratory of Allergic Diseases 2 mast cells in the basal compartment to study the effect of NPs on milk allergen delivery across the epithelial layer, mast cell responses and signaling between epithelial and mast cells in allergenic inflammation. A library of dietary particles (silicon dioxide NPs, titanium dioxide NPs and silver NPs) that varied in particle size, surface chemistry and crystal structures with or without pre-exposure to milk was used in this investigation. Milk-interacted particles were found to acquire surface corona and increased the bioavailability of milk allergens (casein and β-lactoglobulin) across the intestinal epithelial layer. The signaling between epithelial cells and mast cells resulted in significant changes in the early phase and late-phase activation of the mast cells. This study suggested that antigen challenge in mast cells with the presence of dietary NPs may cause the transition of allergic responses from an immunoglobulin E (IgE)-dependent mechanism to a mixed mechanism (both IgE-dependent and IgE-independent mechanisms)., (© 2023 the Australian and New Zealand Society for Immunology, Inc.)

Second near infrared (NIR-II, 1000-1700 nm) fluorescence lifetime imaging is a powerful tool for biosensing, anti-counterfeiting, and multiplex imaging. However, the low photoluminescence quantum yield (PLQY) of fluorescence probes in NIR-II region limits its data collecting efficiency and accuracy, especially in multiplex molecular imaging in vivo. To solve this problem, lanthanide-doped nanoparticles (NPs) β-NaErF 4 : 2%Ce@NaYbF 4 @NaYF 4 with high PLQY and tunable PL lifetime through multi-ion doping and core-shell structural design, are presented. The obtained internal PLQY can reach up to 50.1% in cyclohexane and 9.2% in water under excitation at 980 nm. Inspired by the above results, a fast NIR-II fluorescence lifetime imaging of whole-body vascular in mice is successfully performed by using the homebuilt fluorescence lifetime imaging system, which reveals a murine abdominal capillary network with low background. A further demonstration of fluorescence lifetime multiplex imaging is carried out in molecular imaging of atherosclerosis cells and different organs in vivo through NPs conjugating with specific peptides and different injection modalities, respectively. These results demonstrate that the high PLQY NPs combined with the homebuilt fluorescence lifetime imaging system can realize a fast and high signal-to-noise fluorescence lifetime imaging; thus, opening a road for multiplex molecular imaging of atherosclerosis., (© 2023 Wiley-VCH GmbH.)

Natural nanoscale polysaccharide and its application have attracted much attention in recent years. In this study, we report for the first time that a novel naturally occurring capsular polysaccharide (CPS-605) from Lactobacillus plantarum LCC-605, which can self-assemble into spherical nanoparticles with an average diameter of 65.7 nm. To endow CPS-605 with more functionalities, we develop amikacin-functionalized capsular polysaccharide (CPS) nanoparticles (termed CPS-AM NPs) with improved antibacterial and antibiofilm activities against both Escherichia coli and Pseudomonas aeruginosa. They also exhibit faster bactericidal activity than AM alone. The high local positive charge density of CPS-AM NPs facilitates the interaction between the NPs and bacteria, leading to extraordinary bactericidal efficiencies (99.9 % and 100 % for E. coli and P. aeruginosa, respectively, within 30 min) by damaging the cell wall. Very interestingly, CPS-AM NPs exhibit an unconventional antibacterial mechanism against P. aeruginosa, that is, they can induce plasmolysis, along with bacterial cell surface disruption, cell inclusion release and cell death. In addition, CPS-AM NPs exhibit low cytotoxicity and negligible hemolytic activity, showing excellent biocompatibility. The CPS-AM NPs provide a new strategy for the design of next-generation antimicrobial agents that can reduce the working concentration of antibiotics to fight against bacterial resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Since the hypoxia tumor microenvironment (TME) will not only limit the treatment effect but also cause tumor recurrence and metastasis, intratumoral aggravated hypoxia level induced by vascular embolization is one of the major challenges in tumor therapy. The chemotherapeutic effect of hypoxia-activated prodrugs (HAPs) could be enhanced by the intensified hypoxia, the combination of tumor embolization and HAP-based chemotherapy exhibits a promising strategy for cancer therapy. Herein, an acidity-responsive nanoplatform (TACC NP) with multiple pathways to benefit the hypoxia-activated chemotherapy is constructed by loading the photosensitizer Chlorin e6 (Ce6), thrombin (Thr), and AQ4N within the calcium phosphate nanocarrier via a simple one-pot method. In the acidic TME, TACC NPs could be degraded to release Thr and Ce6, resulting in the destruction of tumor vessels and consumption of intratumoral oxygen under laser irradiation. Therefore, the intratumoral hypoxia level could be significantly aggravated, further leading to the enhanced chemotherapeutic effect of AQ4N. With the guidance of in vivo fluorescence imaging, the TACC NPs exhibited excellent tumor embolization/photodynamic/prodrug synergistic therapeutic effects with good biosafety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

To obtain a green carrier for intestinal targeted delivery, an emulsion gel was designed by the self-assembly between gelatin and Pickering emulsion based on gallic acid modified-chitosan nanoparticles (GCS NPs). The emulsion gels loaded with garlic essential oil (Geo) and curcumin (Cur) were abbreviated as GOEG and GCEG, respectively. Meanwhile, the sodium alginate bead loaded with Geo (GOEGS 3 ) and the bead loaded with Cur (GCEGS) were prepared as controls. Results demonstrated that the emulsion gels significantly improved the bioaccessibility of Geo and Cur, showing great intestinal targeting delivery properties comparable to that of sodium alginate beads. Moreover, Caco-2 cell experiments indicated that GOEG and GCEG displayed good biocompatibility and enhanced cellular uptake of Geo and Cur. The emulsion gels also exhibited excellent anti-inflammatory properties in the lipopolysaccharide-induced cell model, exhibiting great potential for clinical application. This work provides some references for the preparation of multifunctional emulsion gels with excellent delivery performance by a green method., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Although photothermal therapy (PTT) has been widely applied for tumor treatment, tumor cells thermotolerance still limits PTT efficiency. Since the overexpressed HSP90α in tumor cells further enhances thermotolerance and protects them from PTT damage, a new nanoprobe that can specifically detect and downregulate HSP90α mRNA was developed to enhance the PTT effect. Based on the HSP90α mRNA sequence, the nanoprobe Au-DNA1/DNA2 can specifically bind to HSP90α mRNA for recovering its fluorescence and further inhibit the synthesis of HSP90α to reduce tumor heat tolerance. Moreover, another nanoprobe, Au-DNA3, can self-assemble with the Au-DNA1 nanoprobe after the detection to form Au aggregations to enhance PTT afterward for better efficiency. Simultaneously, such a design improves tissue penetration and tumor retention, thereby reducing the damage to the surrounding normal tissues. Both in vitro and in vivo experiments showed that the nanoprobes have excellent tumor diagnosis and cancer treatment capabilities, which is of great significance for clinical translational applications.

Hepatobiliary magnetic resonance imaging (MRI) can inform the diagnosis of liver tumours in patients with liver cirrhosis and hepatitis. However, its clinical utility has been hampered by the lack of sensitive and specific contrast agents, partly because hepatocyte-specific nanoparticles, regardless of their surface ligands, are readily sequestered by Kupffer cells. Here we show, in rabbits, pigs and macaques, that the performance of hepatobiliary MRI can be enhanced by an ultrasmall nanoparticle composed of a manganese ferrite core (3 nm in diameter) and poly(ethylene glycol)-ethoxy-benzyl surface ligands binding to hepatocyte-specific transmembrane metal and anion transporters. The nanoparticle facilitated faster, more sensitive and higher-resolution hepatobiliary MRI than the clinically used contrast agent gadoxetate disodium, a substantial enhancement in the detection rate (92% versus 48%) of early-stage liver tumours in rabbits, and a more accurate assessment of biliary obstruction in macaques. The nanoparticle's performance and biocompatibility support the further translational development of liver-specific MRI contrast agents., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Nanoplastics have become ubiquitous in the global environment and have attracted increasing attention. However, whether there is an influence between exposure to nanoplastics and diabetes is unclear. To determine the effects of exposure to Polystyrene nanoplastics (PS-NPs) and evaluate the underlying mechanisms, mice were orally exposed to PS-NPs at dosages of 1, 10, 30 mg/kg/day for 8 weeks, alone or combined with a high fat diet and streptozocin (STZ) injection. Our data showed that exposure to 30 mg/kg/day PS-NPs alone induced a significant increase in blood glucose, glucose intolerance and insulin resistance. Combined with a high fat diet and STZ injection, PS-NPs exposure markedly aggravated oxidative stress, glucose intolerance, insulin tolerance and insulin resistance, and induced lesions in the liver and pancreas. PS-NPs exposure could decrease the phosphorylation of AKT and GSK3β, and treatment with SC79, a selective AKT activator, could increase the level of AKT and GSK3β phosphorylation, effectively alleviating the increase in ROS levels in the liver or pancreas, and slightly attenuating the increase in fasting blood glucose levels and insulin resistance induced by PS-NPs exposure. This showed that exposure to PS-NPs aggravated type 2 diabetes and the underlying mechanism partly involved in the inhibition of AKT/GSK3β phosphorylation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Commercial nano-scale carbon blacks (CB) are being harnessed widely and may impose potentially hazardous effects because of their unique properties, especially if they have been modified to grow reactive functional groups on their surface. Cytotoxicity of CB has been well studied but the membrane damage mechanisms and role of surface modification are still open to debate. Negatively and positively charged giant unilamellar vesicles (GUVs) were prepared using three lipids as model cell membranes to examine the mechanistic damage of CB and MCB (modified by acidic potassium permanganate) aggregates. Optical images showed that both anionic CB and MCB disrupted the positively charged but not the negatively charged GUVs. This disruption deteriorated with the rise and extension of exposure concentration and time. Lipids extraction caused by CBNs (CB and MCB together are called CBNs) was found. MCB caused more severe disruption than CB. MCB was enveloped into vesicles through an endocytosis-like process at 120 mg/L. MCB mediated the gelation of GUVs, perhaps through C-O-P bonding bridges. The lower hydrodynamic diameter and more negative charges may have been responsible for the distinction effect of MCB over CB. The adhesion and bonding of CBNs to the membrane were favored by electrostatic interaction and the practical application of CBNs warrants more attention.

Use of nanoparticles (NPs) in the food industry raises dietary health concerns. Assessing dietary NPs remains challenged due the vast number of products and the resource-intensive nature of toxicity testing. Advancements in high-throughput transcriptomics, coupled with benchmark dose (BMD) analysis are poised to modernize chemical safety assessments. The study objective was to derive transcriptomic point of departure (tPOD) values for common dietary NPs through dose-response analysis of 3'RNA-sequencing data. Two intestinal cell lines (Caco-2, HIEC-6) were exposed to 9 forms of Ag, SiO 2 , and TiO 2 , and expression of L1000 landmark genes was characterized. In Caco-2 cells, tPOD mode concentrations were 0.4-0.6, 21-32, and 17-59 ppm for NPs of Ag, SiO 2 , and TiO 2 , respectively; in HIEC-6 cells, the respective tPOD values were 6-7, 7-9, and 3-13 ppm. Pathway BMDs across cases identified, for example, osteoclast and Th1/Th2 cell differentiation, and cell cycle, signaling, and senescence pathways. In all cases, the tPOD and pathway BMD values were lower than concentrations associated with cellular changes (e.g., generation of reactive oxygen species and proinflammatory cytokines, and cytotoxicity). These results demonstrate that transcriptomics dose-response analysis using in vitro models can help to increase understanding of a NP's mechanisms of action and derive quantitative information for dietary risk assessment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:SR and JJ are employed at QIAGEN which has commercial interests in the 3’ UPX assays used., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To protect quercetin and address some of the barriers about shellac as a delivery carrier, we investigated the effects of sodium caseinate surface decoration on the formation, stability, and physiochemical properties of shellac nanoparticles (SNPs) for the first time. Herein, 0.3% caseinate was selected to prepare the quercetin-loaded shellac/sodium caseinate complex nanoparticles (SQCNPs), ensuring stable formation of nanoparticles and preventing irreversible aggregation of SNPs in acid. Fourier transform infrared spectroscopy and complex nanoparticle dissociation test indicated SQCNPs were fabricated based hydrophobic and hydrogen-bonding interactions among Que, shellac, and caseinate. Besides, the modification of sodium caseinate can address salt instability and low redispersibility and improve encapsulation efficiency of SNPs. Meanwhile, SQCNPs possessed good antioxidant capacity, low cytotoxicity and controlled release in simulated gastrointestinal digestion. In summary, this work might open up a new, green, and sustainable method to design a bioactive substance delivery system by employing shellac as a vehicle., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Pillar[5]arene-functionalized rhodium nanoparticles (Rh@CPA NPs) are first synthesized via a facile one-pot chemical reduction method. Rh@CPA NPs with good reusability and biocompatibility show excellent catalytic activities in reducing toxic nitrophenols and azo dyes, and also exhibit superior photothermal ablation capability towards Staphylococcus aureus under 808 nm laser irradiation. This work suggests that the supramolecular capping strategy could be used to construct novel hybrid materials for various applications.

Purpose: Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo., Methods: To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo., Results: The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells' formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque., Conclusion: The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Dai et al.)

A pH-responsive cascade nanoplatform based on ZIF-8 disintegrates in the weakly acidic tumor microenvironment to release MnO 2 , CaO 2 and Ce6. The drugs can cyclically generate O 2 for sonodynamic therapy, consume glutathione to tune the redox hemostasis, and produce cytotoxic ˙OH to kill tumor cells via chemical dynamics therapy.

Background: Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback., Methods and Results: In the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed by 1 H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an H 2 O 2 ON/OFF stimulated model. Enhanced release profiles stimulated by H 2 O 2 were verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway., Conclusions: Thus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss., (© 2022. The Author(s).)

Neural regulation techniques play an essential role in the functional dissection of neural circuits and also the treatment of neurological diseases. Recently, a series of nanomaterials, including upconversion nanoparticles (UCNPs), magnetic nanoparticles (MNPs), and silicon nanomaterials (SNMs) that are responsive to remote optical or magnetic stimulation, have been applied as transducers to facilitate localized control of neural activities. In this review, we summarize the latest advances in nanomaterial-mediated neural regulation, especially in a remote and minimally invasive manner. We first give an overview of existing neural stimulation techniques, including electrical stimulation, transcranial magnetic stimulation, chemogenetics, and optogenetics, with an emphasis on their current limitations. Then we focus on recent developments in nanomaterial-mediated neural regulation, including UCNP-mediated fiberless optogenetics, MNP-mediated magnetic neural regulation, and SNM-mediated non-genetic neural regulation. Finally, we discuss the possibilities and challenges for nanomaterial-mediated neural regulation., (© 2022 IOP Publishing Ltd.)

The regulatory functions of plant miRNAs on mammalian bodies are controversial, mainly because stability of the miRNAs in the digestive tract, as the prerequisite for their cross-kingdom effects, has somehow been overlooked. Hence, as the first stage of food ingestion, stability of plant miRNAs in human saliva has been investigated. The results show that plant miRNAs are of considerable resistance against salivary digestion, as surviving miRNAs more than 20 fM are detected. The stability varies dramatically, which can be explained by the difference in tertiary structure, governing their affinities to RNase. Surprisingly, miRNAs of low initial concentrations can end up with high survival rates after digestion. Plant miRNAs can be loaded into exosome-like nanoparticles (ELNs) and microcapsules formed by food components, both of which protect the miRNAs from being degraded in human saliva. Overall, plant miRNAs can apply certain strategies to maintain constant concentrations, paving the way for their potential cross-kingdom effects.

This work investigated the metagenomics-based behavior of antibiotic resistance genes (ARGs) during cattle manure anaerobic digestion with zinc oxide nanoparticles (ZnO NPs) that are commonly used as animal feed additives. The 6.6% decrease in total ARGs abundance while remained unchanged ARGs diversity with ZnO NPs (5 mg/g total solid), suggested ZnO NPs may mitigate ARGs risk by abundance. Also, ZnO NPs affected ARGs with mechanisms specifically of antibiotic inactivation and antibiotic target change, and declined potential hosts' abundance (bacterial genus Ruminiclostridium, Riminococcus, and Paenibacillus) which mainly contributed to the decreased ARGs' abundance. Besides, microbial chemotaxis decreased by 17% with ZnO NPs compared to that without nanoparticles indicated a depression on potential hosts, who could develop the mechanism to adapt to altered digestion conditions, which probably inhibited the ARGs' propagation. These findings are important to promote understanding of the potential ARGs risks in treatments of livestock wastes containing animal feed additives., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity. To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named "PLGA-PEG-poly(I:C)" (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4 + T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1, IgG2c in serum, and sIgA in lung washings. Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFR apt ) modification., Results: Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFR apt -miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFR apt , was developed. In vitro analysis demonstrated that 4WJ-EGFR apt -miR-375-PTX possesses strong thermal and pH stabilities. EGFR apt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFR apt -miR-375-PTX was selectively distributed in tumor sites via EGFR apt -mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity., Conclusion: This strategy may provide a practical approach for targeted therapy of ESCC., (© 2021. The Author(s).)

Implant-associated bacterial infections significantly impair the integration between titanium and soft tissues. Traditional antibacterial modifications of titanium implants are able to eliminate bacteria, but the resulting pro-inflammatory reactions are usually ignored, which still poses potential risks to human bodies. Here, a dual drug-loading system on titanium has been developed via the adhesion of a catechol motif-modified methacrylated gelatin hydrogel onto TiO 2 nanotubes. Then synthesized CaO 2 nanoparticles (NPs) are embedded into the hydrogel, and interleukin-4 (IL-4) is loaded into the nanotubes to achieve both antibacterial and anti-inflammatory properties. The dual drug-loading system can eliminate Staphylococcus aureus (S. aureus) rapidly, attributed to the H 2 O 2 release from CaO 2 NPs. The potential cytotoxicity of CaO 2 NPs is also remarkably reduced after being embedded into the hydrogel. More importantly, with the gradual release of IL-4, the dual drug-loading system is capable of modulating pro-inflammatory reactions by inducing M2 phenotype polarization of macrophages. In a subcutaneous infection model, the S. aureus contamination is effectively resolved after 2 days, and the resulting pro-inflammatory reactions are also inhibited after 7 days. Finally, the damaged tissue is significantly recovered. Taken together, the dual drug-loading system exhibits great therapeutic potential in effectively killing pathogens and inhibiting the resulting pro-inflammatory reactions., (© 2021 Wiley-VCH GmbH.)

Background: It is widely acknowledged that pathogenic germs delay wound healing to some extent. To explore factors influencing the wound healing process, the current study was conducted to evaluate the antibacterial effect of topical application of copper sulfide nanoparticles (CuS NPs) in vitro and on infected wound healing process in the rat model. Materials and Methods: In this study, the morphology and size of CuS NPs were detected. Staphylococcus aureus and Escherichia coli were used so that the antibacterial ability of CuS NPs could be evaluated better. In addition, a 2-cm circular full-thickness wound infected with a solution of 10 7 colony forming units (CFU) Staphylococcus aureus was created on the back of each rat. The rats were divided into four groups including the control group, the 100 mcg/mL CuS NPs group, the 250 mcg/mL CuS NPs group, and the 500 mcg/mL CuS NPs group. Tissue bacterial count and histologic assessment were evaluated. Results: The results indicated that CuS NPs had antibacterial activity against Staphylococcus aureus and Escherichia coli . Moreover, they could decrease the incidence of bacterial colonization and promote wound healing through re-epithelialization and collagen deposition. Furthermore, CuS NPs could maintain Cu 2+ continuous release and inhibit the viability of Staphylococcus aureus through lipid peroxidation. Conclusions: This study found that CuS NPs have fine antibacterial properties, and particularly, the 500 mcg/mL CuS NPs had better effects, without increase of side effects. They could promote infected wound healing, the prospective clinical application of which was further confirmed in the treatment of wound infection.

Nanoparticles (NPs) are increasingly being used in the food sector, yet little is known about the potential health risks associated with oral exposure to dietary NPs. In this study, the most widely used NPs in food industry including food grade silicon dioxide (SiO 2 ), titanium dioxide (TiO 2 ) and silver (Ag), along with their non-food grade and bulk counterparts, are characterized for physicochemical properties and molecular, cellular, and intracellular effects on human intestinal epithelial cells (Caco-2 and HIEC-6). Silver NPs are the most cytotoxic and induce significant cellular changes in oxidative stress, Ca 2+ flux and mitochondria function, leading to cellular junction disruption at the lowest exposure concentration. At higher testing concentrations, NPs but not microparticles of SiO 2 and TiO 2 cause sublethal cellular responses and remodel tight junctions without impairing epithelial integrity. To relate the cellular results to key events in GI disorder progression, NPs are exposed to an in vitro co-culture model for cow's milk allergy comprised of Caco-2 and allergy sera-primed mast cells (LUVA). All particle treatments increase the allergen delivery across intestinal epithelium and subsequent allergy responses. Overall, the study has identified a particle-dependent alteration in intestinal epithelium and highlighted potential safety concerns of dietary NPs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Pulmonary hypertension (PH) is a common complication in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated with mutations in the FOXF1 gene. Although the loss of alveolar microvasculature causes PH in patients with ACDMPV, it is unknown whether increasing neonatal lung angiogenesis could prevent PH and right ventricular (RV) hypertrophy., Methods: We used echocardiography, RV catheterization, immunostaining, and biochemical methods to examine lung and heart remodeling and RV output in Foxf1 WT/S52F mice carrying the S52F Foxf1 mutant embryonic stem cells to differentiate into respiratory cell lineages in vivo was examined using blastocyst complementation. Intravascular delivery of nanoparticles with a nonintegrating Foxf1 WT/S52F mutant embryonic stem cells to differentiate into respiratory cell lineages in vivo was examined using blastocyst complementation. Intravascular delivery of nanoparticles with a nonintegrating Stat3 expression vector was used to improve neonatal pulmonary angiogenesis in Foxf1 WT/S52F mice and determine its effects on PH and RV hypertrophy., Results: Foxf1 WT/S52F mice developed PH and RV hypertrophy after birth. The severity of PH in Foxf1 WT/S52F embryonic stem cells have a propensity to differentiate into pulmonary myofibroblasts. Intravascular delivery of nanoparticles carrying S52F Foxf1 mutation were used to produce chimeras through blastocyst complementation and to demonstrate that Foxf1 WT/S52F embryonic stem cells have a propensity to differentiate into pulmonary myofibroblasts. Intravascular delivery of nanoparticles carrying Stat3 cDNA protected Foxf1 WT/S52F mice from RV hypertrophy and PH, improved survival, and decreased fibrotic lung remodeling., Conclusions: Nanoparticle therapies increasing neonatal pulmonary angiogenesis may be considered to prevent PH in ACDMPV.

Multifunctional nanodrugs have emerged as an effective platform to integrate multiple imaging and therapeutic functions for tremendous biomedical applications. However, the development of a simple potent theranostic nanoplatform is still an intractable challenge. Herein, a novel theranostic nanoplatform was developed by coupling prepared Au nanobipyramids with Gd 2 O 3 , Au nanoclusters and denatured bovine serum albumin (AuNBP-Gd 2 O 3 /Au-dBSA) for FL/MR dual-modal imaging guided photothermal therapy. AS1411 aptamers were conjugated to enhance its targetability towards breast cancer. The AS1411-AuNBP-Gd 2 O 3 /Au-dBSA suspension could be readily heated above 40 °C at a low concentration (2 mg/L) and NIR density (1 W/cm 2 ). The AS1411-AuNBP-Gd 2 O 3 /Au-dBSA revealed a fluorescence quantum yield of 4.2% and higher longitudinal relaxivity rate of 6.75 mM -1  s -1 compared to Gd-DTPA of 4.45 mM -1  s -1 . As a result, the AS1411-AuNBP-Gd 2 O 3 /Au-dBSA functions as a multimodal nanoprobe of photothermal, fluorescence and MR imaging for specific tumor diagnosis and guidance of therapy, which was validated via in vitro and in vivo tests. Moreover, AS1411-AuNBP-Gd 2 O 3 /Au-dBSA nanoparticles indicated excellent photothermal anticancer effect more than 95% in both in vitro and in vivo tests. Besides, the low toxicity of AS1411-AuNBP-Gd 2 O 3 /Au-dBSA nanocomposites was further confirmed in vitro and in vivo. Thus, these results demonstrated the AS1411-AuNBP-Gd 2 O 3 /Au-dBSA nanocomposites as a rational design of multifunctional nanoplatform to enable multimodal imaging guided photothermal therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Studies have shown that a higher GSH level is related to more drug-resistant and invasiveness of a tumor. However, it is a great challenge to accurately imaging the GSH level in vivo , for its imaging intensity will interfered by different accumulation of probes in the tumor. Thus, we hypothesized ratiometric photoacoustic imaging that can be used to predict the drug-resistant and invasiveness of tumors by accurate GSH level imaging. In this study, we synthesized MnO₂/Indocyanine Green (MnO₂/ICG). It can be used as ratiometric photoacoustic (PA) imaging probe, for its absorption at 780 nm (Ab 780 ) can be decreased and 680 nm (Ab 680 ) remain unchanged upon GSH reduction. And our results confirmed that a lower PA absorption ratio (Ab 780 /Ab 680 ) corresponded to a higher GSH level of the tumor. Besides, the near-infrared fluorescence (FI) imaging was used as an assistant, for it can be quenched upon GSH. Therefore, MnO₂/ICG can predict the tumor invasiveness and drug resistance by imaging the GSH level. This study provides reference to predict the prognosis of tumors by imaging the metabolic biomarker of tumors.

As a kind of artificial recognition material, molecularly imprinted polymers (MIPs) offer a promising perspective to be developed as synthetic chemical binders capable of selectively recognize biomacromolecules. However, owing to the large size and conformational flexibility of proteins and peptides, imprinting of these biomacromolecules remains a challenge. Novel imprinting strategies still need exploration for the improvement of recognition performance of MIPs. Herein, we developed a hydrazone bond-oriented surface imprinting strategy for an endogenous peptide hormone, human atrial natriuretic peptide (ANP). Surface-oriented imprinting of peptide via reversible covalent bond anchoring approach increased the orientation homogeneity of imprinted cavities as well as the utility of templates. The prepared nanoparticles exhibited high selectivity and fast recognition kinetics for ANP epitope. The dissociation constant between ANP epitope and MIP was measured as 5.3 μM. The applicability of the material in real samples was verified by the selective magnetic extraction of ANP from human plasma samples. This hydrazone bond-oriented surface imprinting strategy provides an alternative approach for the separation of peptides or proteins in complex bio-samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Energy spectrum computed tomography (CT) can quantify the concentrations of substances in vitro and in vivo. In this study, we designed a single-shell system of doxorubicin (DOX) loaded in zirconium dioxide nanoparticles (DOX@ZrO₂ NPs) as a novel chemotherapy drug delivery system. The concentration of DOX@ZrO₂ NPs in tissue was monitored with energy spectrum CT to calculate the release of DOX from the NPs. The standard curve of the gradient concentrations of ZrO₂ NPs and base material content fit a logarithmic equation. HepG2 cells were incubated with 200 μ mL DOX@ZrO₂ for different times. The concentration in the cells detected with energy spectrum CT correlated strongly with the concentration of chemotherapeutics in the cells ( r = 0.98, P < 0.05). The data indicate that energy spectrum CT is a reliable means of real-time monitoring of the transport of NPs and release of the NP payload in local tissue. The finding could improve the accuracy of clinical imaging and promote the therapeutic use of NPs. Free of clinical trial registeration: There were no animal and human materials involved in this experiment.

An increasing production and use of titanium dioxide nanoparticles (TiO 2 NPs) pose a huge threat to phytoplankton since they are largely released into aquatic environments, which represent a sink for TiO 2 NPs. However, toxicity and protective mechanisms of cyanobacteria in response to TiO 2 NPs remain elusive. Here we investigated toxic effects of two sizes of TiO 2 NPs (50 and 10 nm) and one bulk TiO 2 (200 nm) on a cyanobacterium, Synechocystis sp. and their possible protective mechanisms. We found that 10 nm TiO 2 NPs caused significant growth and photosynthesis inhibition in Synechocystis sp. cells, largely reflected in decreased growth rate (38%), operational PSII quantum yields (40%), phycocyanin (51%) and allophycocyanin (63%), and increased reactive oxygen species content (245%), superoxide dismutase activity (46%). Also, transcriptomic analysis of Synechocystis sp. exposure to 10 nm TiO 2 NPs showed the up-regulation of D1 and D2 protein genes (psbA and psbD), ferredoxin gene (petF) and F-type ATPase genes (e.g., atpB), and the down-regulation of psbM and psb28-2 in PS II. We further proposed a conceptual model to explore possible toxic and protective mechanisms for Synechocystis sp. under TiO 2 nanoparticle exposure. This study provides mechanistic insights into our understanding of Synechocystis sp. responses to TiO 2 NPs. This is essential for more accurate environmental risk assessment approaches of nanoparticles in aquatic ecosystems by governmental environmental agencies worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Clinically, inhibition of both bacterial infection and excessive inflammation is a crucial step for improved wound treatments. Herein, the fabrication of near-infrared-light (NIR)-activatable deoxyribonuclease (DNase)-carbon monoxide (CO)@mesoporous polydopamine nanoparticles (MPDA NPs) is demonstrated for efficient elimination of methicillin-resistant Staphylococcus aureus (MRSA) biofilms and the following anti-inflammatory activity. Specifically, thermosensitive CO-gas-releasing donors (CO releasing molecules, FeCO) are first encapsulated into MPDA NPs, followed by covalently immobilizing deoxyribonuclease I (DNase I) on the surfaces of MPDA NPs. DNase I can degrade the extracellular DNA in biofilms, which site specifically destroys the compactness of the biofilms. With NIR irradiation, DNase-CO@MPDA NPs display great photothermal ability, and further trigger on-demand delivery of bactericidal CO gas that can adequately permeate the impaired biofilms. Eventually, they achieve effective MRSA biofilm elimination in virtue of the synergistic effects of both DNase I participation and CO-gas-potentiated photothermal therapy. Importantly, the inflammatory responses of DNase-CO@MPDA NPs and NIR-treated wounds are simultaneously alleviated owing to the anti-inflammatory features of released CO. Finally, NIR-activatable DNase-CO@MPDA NPs accelerate the healing process of MRSA-biofilm-infected cutaneous wounds. Taken together, this phototherapeutic strategy displays great therapeutic potential in treating the formidable clinical problems caused by MRSA biofilms and the accompanying inflammation., (© 2021 Wiley-VCH GmbH.)

Photodynamic therapy (PDT) efficacy has been dramatically limited by the insufficient oxygen (O 2 ) level in hypoxic tumors. Although various PDT nanosystems have been designed to deliver or produce O 2 in support of reactive oxygen species (ROS) formation, the feature of asynchronous O 2 generation and ROS formation still results in the low PDT efficacy. Herein, thylakoid membranes (TM) of chloroplasts is decorated on upconversion nanoparticles (UCNPs) to form UCTM NPs, aiming at realizing spatiotemporally synchronous O 2 self-supply and ROS production. Upon 980 nm laser irradiation, UC NPs can emit the red light to activate both photosystem-I and photosystem-II of TM, the Z-scheme electronic structure of which facilitates water to produce O 2 and further to singlet oxygen ( 1 O 2 ). UCTM NPs showed excellent biocompatibility, and can effectively remove the hypoxic tumor of mice upon 980 nm laser irradiation. This study develops a new PDT strategy for hypoxic tumor therapy based on photosynthesis., (© 2021 Wiley-VCH GmbH.)