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Nanotechnology could improve the effectiveness and functionality of pesticides, but the size effect of nanopesticides on formulation performance and the related mechanisms have yet to be explored, hindering the precise design and development of efficient and eco-friendly nanopesticides. In this study, two non-carrier-coated imidacloprid formulations (Nano-IMI and Micro-IMI) with identical composition but varying particle size characteristics were constructed to exclude other interferences in the size effect investigation. Nano-IMI and Micro-IMI both exhibited rod-like structures. Specifically, Nano-IMI had average vertical and horizontal axis sizes of 239.5 nm and 561.8 nm, while Micro-IMI exhibited 6.7 μm and 22.1 μm, respectively. Compared to Micro-IMI, the small size effect of Nano-IMI affected the arrangement of interfacial molecules, reduced surface tension and contact angle, thereby improving the stability, dispersibility, foliar wettability, deposition and retention of the nano-system. Nano-IMI exhibited 1.3 times higher toxicity to Aphis gossypii Glover compared to Micro-IMI, attributed to its enhanced foliar utilization efficiency. Importantly, the Nano-IMI did not intensify the toxicity to non-target organism Apis mellifera L. This study systematically elucidates the influence of size effect on key indicators related to the effectiveness and safety, providing a theoretical basis for efficient and safe application of nanopesticides and critical insights into sustainable agriculture and environmental 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 © 2024. Published by Elsevier Inc.)

Tamoxifen (TAM) is a classical anti-estrogenic drug that antagonizes estrogen by competitively binding to estrogen receptor α (ERα). However, drug resistance to TAM remains a significant challenge in breast cancer treatment. In this study, we aimed to design an actively targeted drug delivery system to enhance the proliferation inhibitory effects of TAM on ER positive breast cancer cells. Herein, chitosan (CS) was modified with genistein (GEN) to obtain the actively targeted GEN-CS. The TAM-loaded nanoparticles (TAM-GEN-CS-NPs) were constructed using an ionic-crosslinking method, with GEN-CS as the carrier material and sodium tripolyphosphate (TPP) as the crosslinking agent. As a result, TAM-GEN-CS-NPs exhibited a spherical morphology with an average size of 299.8 nm. The encapsulation efficiency and drug loading content were 85.77% and 14.13 µg/mg, respectively. Compared with free TAM, TAM-GEN-CS-NPs displayed obvious slow-release performance. In vitro cellular assays demonstrated that TAM-GEN-CS-NPs had active targeting and proliferation inhibitory effects on MCF-7 cells. The IC 50 of TAM and TAM-GEN-CS-NPs were 10.25 µg/mL and 7.22 µg/mL, respectively. More importantly, the combination index (CI) value of TAM and GEN was less than 1, indicating synergistic effects. Therefore, TAM-GEN-CS-NPs hold the potential to enhance TAM therapy for breast cancer through active targeting and synergistic treatment strategies., 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 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Context: Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways. However, its low bioavailability and rapid degradation hinder its clinical application., Objective: This review explores the potential of nanoencapsulation to enhance the stability, bioavailability, and therapeutic efficacy of EGCG in cancer treatment., Methods: We searched the PubMed database from 2019 to the present, using 'epigallocatechin gallate', 'EGCG', and 'nanoparticles' as search terms to identify pertinent literature. This review examines recent nano-engineering technology advancements that encapsulate EGCG within various nanocarriers. The focus was on evaluating the types of nanoparticles used, their synthesis methods, and the technologies applied to optimize drug delivery, diagnostic capabilities, and therapeutic outcomes., Results: Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment. Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG. The studies highlighted include those where EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms., Conclusions: Nanoencapsulation of EGCG represents a promising approach in oncology, offering multiple therapeutic benefits over its unencapsulated form. Although the results so far are promising, further research is necessary to fully optimize the design of these nanosystems to ensure their safety, efficacy, and clinical viability.

In this study, starch nanoparticles (SNPs) were prepared by alternate treatments of liquid nitrogen ball milling and ultrasonication. The impact, shear and friction forces produced by ball milling, and acoustic cavitation and shear effects generated by ultrasonication disrupted starch granules to prepare SNPs. The SNPs possessed narrow particle size distribution (46.91-210.52 nm) and low polydispersity index (0.28-0.45). Additionally, the SNPs exhibited the irregular fragments with good uniformity. The relative crystallinity decreased from 34.91 % (waxy corn starch, WCS) to 0-25.91 % (SNPs), and the absorbance ratios of R 1047/1022 decreased from 0.81 (WCS) to 0.60-0.76 (SNPs). The SNPs had lower thermal stability than that of WCS, characterized by a decrease in Td (temperature at maximum weight loss) from 309.39 °C (WCS) to 300.39-305.75 °C (SNPs). Furthermore, the SNPs exhibited excellent swelling power (3.48-28.02 %) and solubility (0.34-0.97 g/g). Notably, oil absorption capacity of the SNPs (9.77-15.67 g/g) was rather greater than that of WCS (1.33 g/g). Furthermore, the SNPs possessed the lower storage modulus (G'), loss modulus (G″) and viscosity than that of WCS. The SNPs with predictable size and high dispersion capability prepared in this study lay a foundation for expanding the application of SNPs., 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.)

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by a positive feedback loop between cytokine storm and macrophages and lymphocytes overactivation, which could serve as a valid therapeutic target for HLH treatment. In this study, the clinically extensively used JAK1/2 inhibitor ruxolitinib was encapsulated into macrophage membrane-coated nanoparticles (M@NP-R) with high drug-loading efficiency for targeted HLH treatment. In vitro and in vivo studies demonstrated that M@NP-R not only efficiently adsorbed extracellular proinflammation cytokines, like IFN-γ and IL-6 to alleviate the cytokine storm, but also effectively dampened macrophage activation and proliferation by intracellular JAK/STAT signaling pathway inhibition. M@NP-R treatment significantly ameliorated the clinical and laboratory manifestations of HLH in mouse models, including trilineage cytopenia, hypercytokinemia, organomegaly, hepatorenal dysfunction, and tissue inflammation. Importantly, M@NP-R significantly enhanced the survival of the lethal HLH mice. Altogether, M@NP-R successfully blocked the positive feedback loop between the cytokine storm and macrophage overactivation by depleting extracellular inflammatory cytokines and inhibiting the intracellular JAK/STAT signaling pathway, both of which worked synergistically in HLH treatment. As ruxolitinib has already been extensively used in clinics with favorable safety, and M@NP is biodegradable and highly biocompatible, M@NP-R has good prospects for clinical translation., 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.)

Ionizable lipid-containing lipid nanoparticles (LNPs) are regarded as promising nonviral vectors for gene therapy delivery systems. Rationale design of the ionizable lipid structure based on initial screening of ionizable lipid molecule libraries combined with systematic comparison and analysis on the physical chemical parameters related to delivery efficiency greatly accelerated the discovery of novel LNP candidates for delivering various nucleic acid therapeutics like mRNAs (mRNAs). Based on the copper-catalyzed azide-alkyne click reaction, which is highly efficient and biocompatible, we were able to obtain the lipid molecule library containing a common triazole moiety between different lipid tails and various substituents as hydrophilic head groups. Herein, we systematically investigated the change of p K a values of different ionizable lipid molecules with different substituents as head groups in the click-based lipid library, mapping the p K a value change to different steps in the process of the LNP assembly and mRNA delivery. Systematic analyses on the data including the p K a value of the ionized lipids and the encapsulation and delivery efficiency of mRNA in LNPs with these ionized lipids provided the possibility of rational design on the head and tail structure for the triazole containing ionized lipids to realize highly efficient delivery of different mRNAs.

The aim of the study was to develop an oral targeting drug delivery system (OTDDS) of oxymatrine (OMT) to effectively treat ulcerative colitis (UC). The OTDDS of OMT (OMT/SA-NPs) was constructed with OMT, pectin, Ca 2+ , chitosan (CS) and sialic acid (SA). The obtained particles were characterized in terms of particle size, zeta potential, morphology, drug loading, encapsulation efficiency, drug release and stability. The average size of OMT/SA-NPs was 255.0 nm with a zeta potential of -12.4 mV. The loading content and encapsulation efficiency of OMT/SA-NPs were 14.65% and 84.83%, respectively. The particle size of OMT/SA-NPs changed slightly in the gastrointestinal tract. The nanoparticles can delivery most of the drug to the colon region. In vitro cell experiments showed that the SA-NPs had excellent biocompatibility and anti-inflammation, and the uptake of SA-NPs by RAW 264.7 cells was time and concentration-dependent. The conjugated SA can help the internalization of NPs into target cells. In vivo experiments showed that OMT/SA-NPs had a superior anti-inflammation effect and the effect of reducing UC, which was attributed to the delivery most of OMT to the colonic lumen, the specific targeting and retention in colitis site and the combined anti-inflammation of OMT and NPs., 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.)

Background: Bufalin (BFL, an active anti-tumor compound derived from toad venom ) is limited in its application due to high toxicity and rapid metabolism of the cardiotonic steroid. Ester prodrug self-assembly nanoparticles have shown significant improved effects in addressing the above-mentioned issues., Methods: An ester bond was formed between linoleic acid and bufalin to synthesize linoleic acid-bufalin prodrug (LeB). The self-assembly nanoparticles (LeB-PSNs) containing different mass ratios of DSPE-PEG2k and prodrug (6:4, 7:3, 8:2, 9:1 and 10:0) were prepared via co-precipitation method and defined as 6:4-PSNs, 7:3-PSNs, 8:2-PSNs, 9:1-PSNs and LeB-PSNs, respectively. Further, the characterization (particle size, zeta potential, surface morphology and stability) of the nanoparticles was carried out. Finally, we evaluated the impact of different ratios of DSPE-PEG2k on the hydrolysis rate, cytotoxicity, cellular uptake, cell migration and proliferation suppression potential of the prodrug nanoparticles., Results: The linoleic acid-bufalin prodrug (LeB) was successfully synthesized. Upon the addition of DSPE-PEG2k at different weight ratios, both particle size and polydispersity index (PDI) significantly decreased, while the zeta potential increased remarkably. No significant differences in particle size, PDI and Zeta potential were observed among the 9:1, 8:2 and 7:3 PSNs. Notably, the 8:2 (w/w) DSPE-PEG2k nanoparticles exhibited superior stability, hydrolysis and cellular uptake rates, along with efficient cell cytotoxicity, cell migration and proliferation suppression., Conclusion: These findings indicate that DSPE-PEG2k could improve the performance of BFL prodrug nanoparticles, namely enhancing stability and achieving adaptive drug release by modulating the hydrolysis rate of esterase. This study therefore provides more opportunities for the development of BFL application., Competing Interests: The authors report no competing interest in this work., (© 2024 Zhang et al.)

Monkeypox virus (MPXV) infection is currently an evolving public health concern, highlighting an urgent need for early and rapid detection of MPXV. Here, we present a diagnostic test called MPXV-LAMP-LFB, which combines loop-mediated isothermal amplification (LAMP) and nanoparticle-based lateral flow biosensor (LFB) for the simple, sensitive and specific detection of MPXV and differentiation of its two clades. The MPXV-LAMP-LFB can be conducted at a heating block and the detection results can be visually indicated with the biosensor without any specialized apparatus. Two sets of LAMP primers targeting the D14L and ATI genes were designed for the Central and West African MPXV isolates, respectively. The optimal amplification condition was 64 °C for 40 min. Thus, the MPXV-LAMP-LFB test can be completed within 1 h, incorporating rapid DNA extraction (∼15 min), LAMP reaction (∼40 min) and result indicating (∼5 min). The MPXV-LAMP-LFB assay could detect down to 5 copies of plasmid template and 12.5 copies of pseudotyped virus in simulated blood samples. Furthermore, the MPXV-LAMP-LFB assay correctly identified all the positive controls and successfully avoided cross-reactivity with the non-MPXV pathogens or clinical samples, demonstrating its high specificity. Overall, the MPXV-LAMP-LFB test developed in this study showed great promise as a rapid, sensitive and accurate molecular tool for diagnosing MPXV infection., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The maintenance of the intestinal barrier is crucial for the overall balance of the gut and the organism. Dysfunction of the intestinal barrier is closely associated with intestinal diseases. In recent years, due to the increased presence of nanoparticles (NPs) in the human diet, there has been a growing concern regarding the safety and potential impact of these NPs on gastrointestinal health. The interactions between food-derived NPs and the intestinal barrier are numerous. This review provides an introduction to the structure and function of the intestinal barrier along with a comprehensive summary of the interactions between food NPs and the intestinal barrier. Additionally, we highlight the potential connection between the food NPs-induced dysfunction of the intestinal barrier and inflammatory bowel disease. Finally, we discuss the enhancement of food NPs on the repair of the intestinal barrier damage and the nutrients absorption. This review holds significant importance in furthering our understanding of the regulatory mechanisms of food-derived NPs on the intestinal barrier.

DNA-based molecular computing has evolved to encompass a diverse range of functions, demonstrating substantial promise for both highly parallel computing and various biomedical applications. Recent advances in DNA computing systems based on surface reactions have demonstrated improved levels of specificity and computational speed compared to their solution-based counterparts that depend on three-dimensional molecular collisions. Herein, computational biomolecular interactions confined by various surfaces such as DNA origamis, nanoparticles, lipid membranes and chips are systematically reviewed, along with their manipulation methodologies. Monitoring techniques and applications for these surface-based computing systems are also described. The advantages and challenges of surface-confined DNA computing are discussed., 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 Inc. All rights reserved.)

Natural plants have acquired an increasing attention in biomedical research. Recent studies have revealed that plant-derived nanoparticles (PDNPs), which are nano-sized membrane vesicles released by plants, are one of the important material bases for the health promotion of natural plants. A great deal of research in this field has focused on nanoparticles derived from fresh vegetables and fruits. Generally, PDNPs contain lipids, proteins, nucleic acids, and other active small molecules and exhibit unique biological regulatory activity and editability. Specifically, they have emerged as important mediators of intercellular communication, and thus, are potentially suitable for therapeutic purposes. In this review, PDNPs were extensively explored; by evaluating them systematically starting from the origin and isolation, toward their characteristics, including morphological compositions, biological functions, and delivery potentials, as well as distinguishing them from plant-derived exosomes and highlighting the limitations of the current research. Meanwhile, we elucidated the variations in PDNPs infected by pathogenic microorganisms and emphasized on the biological functions and characteristics of plant virus nanoparticles. After clarifying these problems, it is beneficial to further research on PDNPs in the future and develop their clinical application value.

Most existing vaccines, delivered by intramuscular injection (IM), are typically associated with stringent storage requirements under cold-chain distribution and professional administration by medical personnel and often result in the induction of weak mucosal immunity. In this context, we reported a microneedle (MN) patch to deliver chitosan oligosaccharide (COS)-encapsulated DNA vaccines (DNA@COS) encoding spike and nucleocapsid proteins of SARS-CoV-2 as a vaccination technology. Compared with IM immunization, intradermal administration via the MN-mediated DNA vaccine effectively induces a comparable level of neutralizing antibody against SARS-CoV-2 variants. Surprisingly, we found that MN-mediated intradermal immunization elicited superior systemic and mucosal T cell immunity with enhanced magnitude, polyfunctionality, and persistence. Importantly, the DNA@COS nanoparticle vaccine loaded in an MN patch can be stored at room temperature for at least 1 month without a significant decrease of its immunogenicity. Mechanically, our strategy enhanced dendritic cell maturation and antiviral immunity by activating the cGAS-STING-mediated IFN signaling pathway. In conclusion, this work provides valuable insights for the rapid development of an easy-to-administer and thermostable technology for mucosal vaccines.

Photothermal therapy (PTT) combined with chemodynamic therapy (CDT) presents an appealing complementary anti-tumor strategy, wherein PTT accelerates the production of reactive oxygen species (ROS) in CDT and CDT eliminates residual tumor tissues that survive from PTT treatment. However, nanomaterials utilized in PTT/CDT are limited by non-specific damage to the entire organism. Herein, a glucose-responsive enzymatic Fe@HRP-ABTS/GOx nanodot is judiciously designed for tumor-specific PTT/CDT via a simple and clean protein-templated biomimetic mineralization synthesis. By oxidizing glucose in tumor cells, glucose oxidase (GOx) activates glucose-responsive tumor therapy and increases the concentration of H 2 O 2 at the tumor site. More importantly, the self-supplied peroxide hydrogen (H 2 O 2 ) can convert ABTS (2,2'-Hydrazine-bis(3-ethylbenzothiazoline-6-sulfonic acid) diamine salt) into oxidized ABTS (oxABTS) through horseradish peroxidase (HRP) catalysis for PTT and photoacoustic (PA) imaging. Furthermore, the Fe 2+ arising from the reduction of Fe 3+ by overexpressed GSH reacts with H 2 O 2 to generate intensely reactive •OH through the Fenton reaction, concurrently depleting GSH and inducing efficient tumor CDT. The in vitro and in vivo experiments demonstrate superior cancer cell killing and tumor eradication effect of Fe@HRP-ABTS/GOx nanodot under near-infrared (NIR) laser irradiation. Collectively, the nanodots provide mutually reinforcing catalytic PTT/CDT anti-tumor strategies for treating liver cancer and potentially other malignancies. STATEMENT OF SIGNIFICANCE: Combinatorial antitumor therapy with nanomedicines presents great prospects for development. However, the limitation of non-specific damage to normal tissues hinders its further clinical application. In this work, we fabricated tumor-selective biomimetic Fe@HRP-ABTS/GOx nanodots for H 2 O 2 self-supplied catalytic photothermal/chemodynamic therapy of tumors. The biomimetic synthesis strategy provides the nanodots with enzymatic activity in response to glucose to produce H 2 O 2 . The self-supplied H 2 O 2 initiates photothermal therapy with oxidized ABTS and enhances chemodynamic therapy through simultaneous •OH generation and GSH depletion. Our work provides a new paradigm for developing tumor-selective catalytic nanomedicines and will guide further clinical translation of the enzymatic biomimetic synthesis strategy., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Engineered collaborative size regulation and shape engineering of multi-functional nanomaterials (NPs) offer extraordinary opportunities for improving the analysis performance. It is anticipated to address the difficulty in distinguishing color changes caused by subtle variations in target concentrations, thereby facilitating the highly sensitive analysis of lateral flow immunoassays (LFIAs). Herein, tremella-like gold-manganese oxide (Au-MnO x ) nanoparticles with precise MnCl 2 regulation are synthesized as immuno signal tracers via a facile one-step redox reaction in alkaline condition at ambient temperature. Avail of the tunable elemental composition and anisotropy in morphology, black-colored tremella-like Au-MnO x exhibits superb colorimetric signal brightness, enhanced antibody coupling efficiency, marvelous photothermal performance, and unrestricted immunological recognition affinity, all of which facilitate highly sensitive multi-signal transduction patterns. In conjunction with the handheld thermal reader device, a bimodal-type LFIA that combines size-regulation- and shape-engineering-mediated colorimetric-photothermal dual-response assay (coined as the SSCPD assay) with a limit of detection of 0.012 ng mL -1 for ractopamine (RAC) monitoring is achieved by integrating Au-MnO x with the competitive-type immunoreaction. This work illustrates the effectiveness of this strategy for establishing high-performance sensing, and the SSCPD assay may be extended to a wide spectrum of future point-of-care (POC) diagnostic applications., (© 2023 Wiley-VCH GmbH.)

Transfer of CeO 2 engineered nanoparticles (NPs) through feces was investigated between two omnivorous organisms, red crucian carp (Carassius auratus red var.) and crayfish (Procambarus clarkii). Upon water exposure (5 mg/L, 7 days), the highest bioaccumulation was observed in carp gills (5.95 μg Ce/g D.W.) and crayfish hepatopancreas (648 μg Ce/g D.W.), with the bioconcentration factors (BCFs) at 0.45 and 3.61, respectively. In addition, 97.4% and 73.0% of ingested Ce were excreted by carp and crayfish, respectively. The feces of carp and crayfish were collected and fed to crayfish and carp, respectively. After feces exposure, bioconcentration was observed in both carp (BCF, 3.00) and crayfish (BCF, 4.56). After feeding crayfish with carp bodies (1.85 μg Ce/g D.W.), CeO 2 NPs were not biomagnified (biomagnification factor, 0.28). Upon water exposure, CeO 2 NPs were transformed into Ce(III) in the feces of both carp (24.6%) and crayfish (13.6%), and the transformation was stronger after subsequent feces exposure (100% and 73.7%, respectively). Feces exposure lowered histopathological damage, oxidative stress, and nutritional quality (e.g., crude proteins, microelements, amino acids) to carp and crayfish in comparison with water exposure. This research highlights the importance of feces exposure on the transfer and fate of NPs in aquatic ecosystems., 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.)

New nanocarrier technologies are emerging, and they have great potential for improving drug delivery, targeting efficiency and bioavailability. Virus-like particles (VLPs) are natural nanoparticles from animal and plant viruses and bacteriophages. Hence, VLPs present several great advantages, such as morphological uniformity, biocompatibility, reduced toxicity and easy functionalisation. VLPs can deliver many active ingredients to the target tissue and have great potential as a nanocarrier to overcome the limitations associated with other nanoparticles. This review will focus primarily on the construction and applications of VLPs, particularly as a novel nanocarrier to deliver active ingredients. Herein, the main methods for the construction, purification and characterisation of VLPs, as well as various VLP-based materials used in delivery systems are summarised. The biological distribution of VLPs in drug delivery, phagocyte-mediated clearance and toxicity are also discussed.

H uman s erum a lbumin (HSA) is a highly water-soluble protein with 67% alpha-helix content and three distinct domains (I, II, and III). HSA offers a great promise in drug delivery with enhanced permeability and retention effect. But it is hindered by protein denaturation during drug entrapment or conjugation that result in distinct cellular transport pathways and reduction of biological activities. Here we report using a protein design approach named r everse- QTY (rQTY) code to convert specific hydrophilic alpha-helices to hydrophobic to alpha-helices. The designed HSA undergo self-assembly of well-ordered nanoparticles with highly biological actives. The hydrophilic amino acids, asparagine (N), glutamine (Q), threonine (T), and tyrosine (Y) in the helical B-subdomains of HSA were systematically replaced by hydrophobic leucine (L), valine (V), and phenylalanine (F). HSA rQTY nanoparticles exhibited efficient cellular internalization through the cell membrane albumin binding protein GP60, or SPARC ( s ecreted p rotein, a cidic and r ich in c ysteine)-mediated pathways. The designed HSA rQTY variants displayed superior biological activities including: i) encapsulation of drug doxorubicin, ii) receptor-mediated cellular transport, iii) tumor cell targeting, and iv) antitumor efficiency compare to denatured HSA nanoparticles. HSA rQTY nanoparticles provided superior tumor targeting and antitumor therapeutic effects compared to the albumin nanoparticles fabricated by antisolvent precipitation method. We believe that the rQTY code is a robust platform for specific hydrophobic modification of functional hydrophilic proteins with clear-defined binding interfaces.

Polystyrene nano-plastics (PS-NPs) can be accumulated in the food chain and can penetrate biological barriers to affect multiple physiological functions. However, the adverse effects of nano-plastics on mammals and the underlying mechanism still remain unknown. To fill the gaps, our study administrated low-dose PS-NPs (50 and 100 μg/L) for 24 consecutive weeks in rats. Behavioral and morphological evaluations were performed to assess the neurobehavoirs. A combined analysis of multiple omics was used to evaluate the dysfunctions of the gut-microbe-brain axis. After dihydrochalcone(NHDC) treatment in the PS-NPs rat model, the inflammation response and apoptosis process were assessed and proteomics was used to explore the underlying mechanism. Our results indicated that long-term exposure to low-dose PS-NPs could induce abnormal neurobehaviors and amygdaloid nucleus impairment, and stimulate inflammatory responses and apoptosis. Metagenomics results revealed that four microbial phyla including Proteobacteria, Firmicutes, Defferibacteres, and Bacteroidetes changed significantly compared to the control. Targeted metabolomics analysis in the feces showed alteration of 122 metabolites induced by the PS-NPs exposure, among which the content of dihydrocaffeic acid was significantly associated with the different microbial genera and pivotal differential metabolites in the amygdaloid nucleus. And NHDC treatment significantly alleviated PS-NP-induced neuroinflammation and apoptosis and the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/phosphorylated cAMP-response element binding protein(p-CREB)/plasma membrane calcium-transporting ATPase 2(Atp2b2) signaling pathway was identified in the proteomics. In conclusion, long-term exposure to low-dose PS-NPs has adverse effects on emotion through the dysregulation of the gut-brain axis, and dihydrocaffeic acid can alleviate these effects via the cAMP/PKA/p-CREB/Atp2b2 signaling pathway., 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.)

Radioenhancing nanoparticles (NPs) are being evaluated in ongoing clinical trials for various cancers including head and neck, lung, esophagus, pancreas, prostate, and soft tissue sarcoma. Supported by decades of preclinical investigation and recent randomized trial data establishing clinical activity, these agents are poised to influence future multimodality treatment paradigms involving radiotherapy. Although the physical interactions between NPs and ionizing radiation are well characterized, less is known about how these agents modify the tumor microenvironment, particularly regarding tumor immunogenicity. In this review, we describe the key multidisciplinary considerations related to radiation, surgery, immunology, and pathology for designing radioenhancing NP clinical trials. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease., (© 2022 Wiley Periodicals LLC.)

There is mounting experimental evidence that blocking angiotensin receptor type 1 activity can prevent the occurrence of hypertension in spontaneously hypertensive rats. Studies have proved this strategy via evasive means, such as intracerebrovascular injections, making clinical translation difficult. This study aimed to develop penetratin and transferrin functionalized liposomes as a delivery tool to safely deliver losartan potassium (an angiotensin receptor blocker) to the brain. Penetratin and transferrin functionalized losartan-loaded liposomes were prepared via the post-insertion technique. Losartan-loaded liposomes were cationic, approximately 150 nm in size, entrapping 66.8 ± 1.5% of losartan. All formulations were well tolerated and internalized by primary and cultured cells in 4 h. Further, the ability to deliver losartan potassium across the blood-brain barrier was evaluated in vivo in Wistar Kyoto rats either in solution or when encapsulated within liposomal nanoparticles. Upon intravenous administration, we did not find a detectable amount of losartan in the brain tissue of rats that received free losartan solution. Contrarily, liposome formulations could deliver losartan to the brain, with a brain AUC and mean resident time of 163.304 ± 13.09 and 8.623 h ± 0.66, respectively. In addition, no toxicity was observed in the animals that received the losartan-loaded liposomes., 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.)

Hepatocellular carcinoma (HCC) is a common digestive tract malignancy that seriously threatens human life and health. Early HCC may be treated by intervention, surgery, and internal radiotherapy, while the choice for late HCC is primarily chemotherapy to prolong patient survival. Lenvatinib (LT) is a Food and Drug Administration (FDA)-approved frontline drug for the treatment of advanced liver cancer and has achieved excellent clinical efficacy. However, its poor solubility and severe side effects cannot be ignored. In this study, a bionic nanodrug delivery platform was successfully constructed. The platform consists of a core of Lenvatinib wrapped with a pH-sensitive polymer, namely, poly(β-amino ester)-polyethylene glycol-amine (PAE-PEG-NH 2 ), and a shell formed by a cancer cell membrane (CCM). The prepared nanodrugs have high drug loading capacity, long-term stability, good biocompatibility, and a long retention time. In addition, the targeting effect of tumor cell membranes and the pH-responsive characteristics of the polymer materials enable them to precisely target tumor cells and achieve responsive release in the tumor microenvironment, which makes them suitable for effective drug delivery. In vivo experiments revealed that the nanodrug showed superior tumor accumulation and therapeutic effects in subcutaneous tumor mice model and could effectively eliminate tumors within 21 days. As a result, it opens up a new way to reduce side effects and improve the specific therapeutic effect of first-line clinical medications to treat tumors., 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.)

Ovarian cancer (OC) ranks first among gynecologic malignancies in terms of mortality. The benefits of poly (ADP-ribose) polymerase (PARP) inhibitors appear to be limited to OC with BRCA mutations. Concurrent administration of WEE1 inhibitors (eg, adavosertib (Ada)) and PARP inhibitors (eg, olaparib (Ola)) effectively suppress ovarian tumor growth regardless of BRCA mutation status, but is poorly tolerated. Henceforth, we aimed to seek a strategy to reduce the toxic effects of this combination by taking advantage of the mesoporous polydopamine (MPDA) nanoparticles with good biocompatibility and high drug loading capacity. In this work, we designed a tumor-targeting peptide TMTP1 modified MPDA-based nano-drug delivery system (TPNPs) for targeted co-delivery of Ada and Ola to treat OC. Ada and Ola could be effectively loaded into MPDA nanoplatform and showed tumor microenvironment triggered release behavior. The nanoparticles induced more apoptosis in OC cells, and significantly enhanced the synergy of combination therapy with Ada plus Ola in murine OC models. Moreover, the precise drug delivery of TPNPs towards tumor cells significantly diminished the toxic side effects caused by concurrent administration of Ada and Ola. Co-delivery of WEE1 inhibitors and PARP inhibitors via TPNPs represents a promising approach for the treatment of OC. STATEMENT OF SIGNIFICANCE: Combination therapy of WEE1 inhibitors (eg, Ada) with PARP inhibitors (eg, Ola) effectively suppress ovarian tumor growth regardless of BRCA mutation status. However, poor tolerability limits its clinical application. To address this issue, we construct a tumor-targeting nano-drug delivery system (TPNP) for co-delivery of Ada and Ola. The nanoparticles specifically target ovarian cancer and effectively enhance the antitumor effect while minimizing undesired toxic side effects. As the first nanomedicine co-loaded with a WEE1 inhibitor and a PARP inhibitor, TPNP-Ada-Ola may provide a promising and generally applicable therapeutic strategy for ovarian cancer patients., 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 © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The current outbreak of monkeypox virus (MPXV) has become a public health emergency of international concern that highlights the need for rapid, sensitive MPXV diagnostic assays. Here, we combined isothermal multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow biosensor (LFB) to devise a diagnostic test for the diagnosis of MPXV infection (called MPXV-MCDA-LFB) and differentiation of West and Central African MPXV isolates. The MPXV-MCDA-LFB protocol conducts isothermal MCDA reaction for DNA templates followed by LFB detection of preamplification target sequences. Two MCDA primer sets were designed targeting the D41L and ATI genes of Central and West African MPXV isolates, respectively, and the optimal condition of two MCDA reactions was 64°C for 30 min. The two MCDA reactions were decoded by LFB, which was devised for detecting three targets, including two amplicons yielded from two MCDA reactions and a chromatography control. Thus, the MPXV-MCDA-LFB assay could be completed within 50 min including rapid template preparation (15 min), MCDA reaction (30 min) and reporting of result (<5 min). The MPXV-MCDA-LFB method is very sensitive and can detect the target genes (D14L and ATI) with as low as five copies of plasmid template per reaction and 12.5 copies of pseudotyped virus in human blood samples. The MPXV-MCDA-LFB assay does not cross-react with non-MPXV templates, validating its specificity. Therefore, the MPXV-MCDA-LFB assay developed here is a useful tool for rapid and reliable diagnosis of MPXV infection., (© 2023 Wiley Periodicals LLC.)

Lipid nanoparticle (LNP)-based mRNA delivery holds promise for the treatment of inherited retinal degenerations. Currently, LNP-mediated mRNA delivery is restricted to the retinal pigment epithelium (RPE) and Müller glia. LNPs must overcome ocular barriers to transfect neuronal cells critical for visual phototransduction, the photoreceptors (PRs). We used a combinatorial M13 bacteriophage-based heptameric peptide phage display library for the mining of peptide ligands that target PRs. We identified the most promising peptide candidates resulting from in vivo biopanning. Dye-conjugated peptides showed rapid localization to the PRs. LNPs decorated with the top-performing peptide ligands delivered mRNA to the PRs, RPE, and Müller glia in mice. This distribution translated to the nonhuman primate eye, wherein robust protein expression was observed in the PRs, Müller glia, and RPE. Overall, we have developed peptide-conjugated LNPs that can enable mRNA delivery to the neural retina, expanding the utility of LNP-mRNA therapies for inherited blindness.

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8 + T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors., 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 © 2022. Published by Elsevier B.V.)

The ability of some animals to rapidly change their colors can greatly improve their chances of escaping predators or hunting prey. A classic example is cephalopods, which can rapidly shift through a wide range of colors. This ability is based on the synergetic effect of the change of pigmentary and structural colors exhibited by their own two categories of color-changing cells: supernatant chromatophores offer various pigmentary colors and lower iridophores or leucophores reflect the different structural colors by adjusting their periodicities. Here, a mechanochromic liquid crystalline elastomer with force-induced synergetic pigmentary and structural color change, whose mechanosensitivity is enhanced by the stress-concentration induced by the doped nanoparticle, is presented. The materials have a large color-changing gamut and high mechanochromic sensitivity, which exhibit great potential in the field of mechanical detectors, sensors, and anti-counterfeiting materials., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Nanoplastic is recognized as an emerging environmental pollutant due to the anticipated ubiquitous distribution, increasing concentration in the ocean, and potential adverse health effects. While our understanding of the ecological impacts of nanoplastics is still limited, we benefit from relatively rich toxicological studies on other nanoparticles such as nano metal oxides. However, the similarity and difference in the toxicokinetic and toxicodynamic aspects of plastic and metallic nanoparticles remain largely unknown. In this study, juvenile Pacific white shrimp Litopenaeus vannamei was exposed to two types of nanoparticles at environmentally relative low and high concentrations, i.e., 100 nm polystyrene nanoplastics (nano-PS) and titanium dioxide nanoparticles (nano-TiO 2 ) via dietary exposure for 28 days. The systematic toxicological evaluation aimed to quantitatively compare the accumulation, excretion, and toxic effects of nano-PS and nano-TiO 2 . Our results demonstrated that both nanoparticles were ingested by L. vannamei with lower egestion of nano-TiO 2 than nano-PS. Both nanoparticles inhibited the growth of shrimps, damaged tissue structures of the intestine and hepatopancreas, disrupted expression of immune-related genes, and induced intestinal microbiota dysbiosis. Nano-PS exposure caused proliferative cells in the intestinal tissue, and the disturbance to the intestinal microbes was also more serious than that of nano-TiO 2 . The results indicated that the effect of nano-PS on the intestinal tissue of L. vannamei was more severe than that of nano-TiO 2 with the same particle size. The study provides new theoretical basis of the similarity and differences of their toxicity, and highlights the current lack of knowledge on various aspects of absorption, distribution, metabolism, and excretion (ADME) pathways of 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 © 2022 Elsevier Ltd. All rights reserved.)

Chitosan (CS) and pea protein isolate (PPI) were used as raw materials to prepare nanoparticles. The structures and functional properties of the nanoparticles with three ratios (1:1, 1:2 1:3, CS:PPI) were evaluated. The particle sizes of chitosan-pea protein isolate (CS-PPI) nanoparticles with the ratios of 1:1, 1:2, and 1:3 were 802.95 ± 71.94, 807.10 ± 86.22, and 767.75 ± 110.10 nm, respectively, and there were no significant differences. Through the analysis of turbidity, endogenous fluorescence spectroscopy and Fourier transform infrared spectroscopy, the interaction between CS and PPI was mainly caused by electrostatic mutual attraction and hydrogen bonding. In terms of interface properties, the contact angles of nanoparticles with the ratio of 1:1, 1:2, and 1:3 were 119.2°, 112.3°, and 107.0°, respectively. The emulsifying activity (EAI) of the nanoparticles was related to the proportion of protein. The nanoparticle with the ratio of 1:1 had the highest potential and the best thermal stability. From the observation of their morphology by transmission electron microscopy, it could be seen that the nanoparticles with a ratio of 1:3 were the closest to spherical. This study provides a theoretical basis for the design of CS-PPI nanoparticles and their applications in promoting emulsion stabilization and the delivery of active substances using emulsions.

Background: Emamectin benzoate (EMB), a frequently used biopesticide, is poorly soluble in water, making it difficult to wet the leaf surface, is prone to degrade in sunlight and readily loses its bioactivity. Traditional methods such as organic solvent application, pH adjustment and addition of photoprotectants either increase the economic and environmental costs or barely achieve the desired goal. We hypothesized that nanotechnology could improve the solubility, foliar affinity, photostability and bioactivity of EMB. This research set out to prepare a nano-EMB solid powder (nano-EMB-SP) and test this hypothesis., Results: Nano-EMB-SP was prepared using a self-emulsifying method combined with carrier solidification. The mean particle size and Polydispersity index (PDI) of nano-EMB-SP were 14.64 nm and 0.24, respectively. A scanning electron microscopy image showed that EMB nanoparticles were mainly spherical or ellipsoidal in shape. Without organic solvent, the aqueous solubility of EMB in nano-EMB-SP was 4500 mg L -1 , at least 14-fold that of the EMB soluble granule (EMB-SG), which is solubilized by pH adjustment. Excellent foliar affinity of EMB was achieved by nano-EMB-SP, which completely wet and penetrated the superhydrophobic surface of cabbage (Brassica oleracea L.) leaf. Without photoprotectants, up to 82% of EMB content can be protected from ultraviolet (UV) damage in nano-EMB-SP. The combined effects of excellent photostability and foliar affinity of nano-EMB-SP led to the bioactivity of EMB being almost unchanged before and after UV radiation., Conclusion: Nano-EMB-SP is an eco-friendly and efficient way to improve the solubility, foliar affinity, photostability and bioactivity of EMB. This research provides a good approach to improving the efficacy of poorly soluble and UV-sensitive pesticides. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.

Mycoplasma pneumoniae ( MP ), the causative agent of MP pneumonia (MPP), has posed a substantial burden to public health owing to a lack of rapid and effective diagnostic methods. Here, we designed a loop-mediated isothermal amplification (LAMP)-based assay, termed LAMP, combined with a nanoparticle-based lateral flow biosensor (LAMP-LFB) for rapid and sensitive diagnosis of MP. -LAMP-LFB included a set of six primers targeting the community-acquired respiratory distress syndrome (CARDS) toxin gene and was performed optimally at 63°C for only 30 min. The resulting LAMP products could be visually indicated by LFB within 2 min, thus the whole process could be accomplished within an hour. MP -LAMP-LFB's sensitivity was 50 fg per reaction, which was in complete accordance with these results obtained from real-time turbidity and visual detection reagent (VDR). MP -LAMP-LFB had no cross-reactivity with other pathogens that had similar clinical presentations. Our assay was further validated using 100 nasopharyngeal swab samples collected from children suspected of MPP, and the result was compared with the real-time PCR method. With a positive rate of 50%, the data indicated that MP -LAMP-LFB is a sensitive test for MP detection in clinical settings. Collectively, the MP -LAMP-LFB assay targeting the CARDS toxin gene was a rapid, highly sensitive, and specific test that could be widely applied in point-of-care settings and basic medical facilities in rural areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, Zhou, Sun, Huang, Zheng, Fu, Jia, Xu, Cui and Wang.)

Rheumatoid arthritis (RA) is a chronic and symmetrical autoimmune disease that primarily characterized with articular synovial hyperplasia, joint swelling, cartilage and bone destruction. The in-depth understanding of the role of immune signaling pathway inhibitors provides inspiration for the construction of new and more effective strategy for RA therapy. In this study, by loading methotrexate (MTX) into an acetalated dextran biopolymer, AcDEX, we developed a pH-sensitive, MTX-loaded and molecularly targeted nanodrug MTX@pH-AcDEX NPs) to decrease the toxicity of MTX and simultaneously enhance its therapeutic effect. The resultant MTX@pH-AcDEX NPs showed the spherical morphology and notable pH-responsiveness with high drug loading of 88.32%. As demonstrated in vitro and in vivo, the reduced cytotoxicity of both RAW264.7 cells and LPS-activated RAW264.7 cells treated with MTX@pH-AcDEX NPs was found compared to free MTX. Upon intravenous administration into adjuvant-induced arthritis (AIA) rat model, the nanodrug had potent pharmacokinetic and pharmacodynamic profiles, which can accumulate in RA lesions and release MTX inhibitors for regulating the JAK-STAT pathways. As a result, the MTX@pH-AcDEX NPs achieved the cartilage and bone protective and a better anti-inflammatory effect with negligible systemic toxicity, suggesting the strong potential of safe and effective nanodrug for RA therapy as well as other autoimmune diseases., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The rapid development of nanotechnology boosts the massive production and utilization of various nanoparticles (NPs). However, the NPs escaped into environments form emergent pollutants, which pose a potential threat to marine organisms and ecosystems. Due to their sessile filter-feeding lifestyle, marine bivalves live in pollution-prone coastal areas are more susceptible to land-sourced pollutants such as NPs. However, the impacts of many NPs on the metabolism, one of the most critical physiological processes of an organism, still remain largely unknown in bivalve species. To fill up this knowledge gap, in this study the impacts of four commonly used NPs (nZnO, nFe 2 O 3 , nCuO, and multi-walled carbon tube (MWCNT)) on the filtration rate, oxygen consumption rate, ammonia excretion rate, and O:N ratio were investigated in the blood clam, Tegillarca granosa. In addition, the expressions of ten key metabolism-related genes upon exposure to these NPs were also analyzed. The results demonstrated that exposure of blood clams to the NPs resulted in a reduction in the food intake (indicated by declined filtration rate), a shift in the metabolism substance, and disruptions in key metabolism-related molecular pathways (i.e., glycolysis and tricarboxylic acid cycle), which may render blood clam in energy shortage and thus pose significant threat to the health of this important bivalve species., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

With the advantages of deep tissue penetration and controllability, external X-ray-induced photodynamic therapy (X-PDT) is highly promising for combined cancer therapy. In addition to the low efficiency of photosensitizer (PS) delivery to tumor sites, however, the radiation- and drug-resistance of hypoxic cells inside the tumor after X-PDT also limit its benefits. Herein, we develop a combined therapeutic modality based on an intelligent nanosized platform ( DA TAT-NP VT ) with tumor acidity-activated TAT presenting and redox-boosted release of tirapazamine (TPZ) for more precise and synchronous X-PDT and selective hypoxia-motivated chemotherapy. After DA TAT-NP VT has accumulated in tumor tissues via decreased blood clearance by masking of the TAT ligand, its targeting ability is reactivated by tumor pH (∼6.8), which enhances tumoral cellular uptake. Upon low-dose X-ray irradiation, the encapsulated verteporfin (VP) generates reactive oxygen species (ROS) to carry out X-PDT against MDA-MB-231 breast tumors. As a result of the abundant GSH-triggered degradation of ditelluride bridged bonds, the cascaded TPZ release and activation in the hypoxic environment following X-PDT would produce highly cytotoxic radicals to serve as antitumor agents to kill the remaining hypoxic tumor cells. This concept provides new avenues for the design of hierarchical-responsive drug delivery systems and represents a proof-of-concept combinatorial tumor treatment.

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants., (© 2022. The Author(s).)

Pesticide compounding technology for disease and pest control emerges as an effective way to increase the effectiveness of pesticides while reducing pesticides resistance. Nanomaterials and encapsulation technology have offered a new insight into preparing efficient pesticide formulations, especially constructing a co-delivery nanoparticle for synergistic pesticides. In this study, a dinotefuran/avermectin co-delivery nanoparticles (DACNPs) against pear tree pests with polylactic acid (PLA) as the wall material were constructed by double-emulsion method combined with high-pressure homogenization technique. The drug content of the DACNPs was 39.1% with an average size of 245.7 ± 4.2 nm and the mean polymer dispersity index (PDI) value was 0.123. The DACNPs showed high foliar retention and good spread performance on target leaves due to the nanoscale effect. The obtained DACNPs showed a better control effect on Grapholitha molesta Busck and Psylla chinensis Yang et Li compared with the commercial formulations, which could significantly prolong the effective duration and enhance the bioactivity with lower amounts and application frequency of pesticides. This study may provide new insights into developing novel pesticide formulations to improve the utilization rate of pesticides, reduce environmental pollution and minimize the cost of farming., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has led to millions of deaths worldwide. Streptococcus pneumoniae (S. pneumoniae) remains a major cause of mortality in underdeveloped countries. A vaccine that prevents both SARS-CoV-2 and S. pneumoniae infection represents a long-sought "magic bullet". Herein, a nanoparticle vaccine, termed SCTV01B, is rationally developed by using the capsular polysaccharide of S. pneumoniae serotype 14 (PPS14) as the backbone to conjugate with the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. The final formulation of conjugated nanoparticles in the network structure exhibits high thermal stability. Immunization with SCTV01B induces potent humoral and Type 1/Type 2 T helper cell (Th1/Th2) cellular immune responses in mice, rats, and rhesus macaques. In particular, SCTV01B-immunized serum not only broadly cross-neutralizes all SARS-CoV-2 variants of concern (VOCs), including the most recent Omicron variant, but also shows high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. Finally, SCTV01B vaccination confers protection against challenges with the SARS-CoV-2 mouse-adapted strain and the original strain in established murine models. Collectively, these promising preclinical results support further clinical evaluation of SCTV01B, highlighting the potency of polysaccharide-RBD-conjugated nanoparticle vaccine platforms for the development of vaccines for COVID-19 and other infectious diseases., (© 2022 Wiley-VCH GmbH.)

Chemodynamic therapy has been appealing for effective cancer treatment. Particularly, Fenton-like reactions catalyzed by Cu 2+ -based nanoparticles showed promising prospects. Herein, we fabricated copper-selenocysteine quantum dots (Cu-Sec QDs) with the majority of Cu + by a facile and robust thermal titration process. No high temperature or pressure is needed for this synthetic route of QDs. The selenocysteine functioned as the reducing agent as well as the stabilizer, circumventing the poor water solubility and stability, leading to enhanced biocompatibility. The existence of Cu + endowed the QDs the ability to catalyze the Fenton-like reaction without an extra reduction reaction of Cu 2+ to Cu + . Moreover, the strong absorption in the near-infrared-II region (1000-1300 nm) of the final Cu-Sec QDs is in great favor of the chemodynamic therapy via the photothermally enhanced Fenton-like reaction. And the Cu-Sec QDs exhibited obvious cytotoxicity to various cancer cell lines. We believe that this facile and robust synthetic approach could open up another method for the fabrication of quantum dots toward the potential Fenton-like reaction-based applications in biological fields.

Glioblastoma (GBM) is the most lethal primary intracranial tumor because of its high invasiveness and recurrence. Therefore, nanocarriers with blood-brain barrier (BBB) penetration and transcranial-controlled drug release and activation are rather attractive options for glioblastoma treatment. Herein, we designed a multifunctional nanocarrier (T- TK NP VP ) that combined targeted X-ray-induced photodynamic therapy (X-PDT) and cascaded reactive oxygen species (ROS)-boosted chemotherapy. The T- TK NP VP loaded with verteporfin (VP) and paclitaxel (PTX) was self-assembled from an angiopep-2 (Ang) peptide, functionalized Ang-PEG-DSPE and ROS-sensitive PEG-TK-PTX conjugate. After systemic injection, the T- TK NP VP efficiently crossed the BBB and targeted the GBM cells via receptor-mediated transcytosis. Upon X-ray irradiation, they can generate a certain amount of ROS, which not only induces X-PDT but also locoregionally activates PTX release and action by cleaving the TK bridged bonds. As evidenced by 9.4 T MRI and other experiments, such nanocarriers offer significant growth inhibition of GBM in situ and prolong the survival times of U87-MG tumor-bearing mice. Taken together, the designed T- TK NP VP provided an alternative avenue for realizing transcranial X-PDT and X-ray-activated chemotherapy for targeted and locoregional GBM treatment in vivo .

Copper and Zinc oxides nanoparticles (CuO and ZnO NPs, respectively) are among the most produced and commonly used engineered nanomaterials. They can be released into the environment, thereby causing health concerns and risks to biodiversity that indicate a need to evaluate their toxicological effects in a complex situation. Here, we used the insect model organism silkworm Bombyx mori to address the concerns about the biological effects associated with dietary exposure of CuO and ZnO NPs. ICP-MS analysis revealed significant accumulation of Cu and Zn (the latter being more accumulated) in silkworms' tissues (gut, fat body, silk gland, and malpighian tubule), and some elimination through feces in the respective NPs-exposed groups. NPs-exposures led to a decrease in larval body mass, survivorship, and cocoon production, where the effects of ZnO NPs were more pronounced. We also found that NPs-exposure induced gene expression changes (Attacin, lysozyme, SOD, and Dronc) and altered the activities of antioxidant enzymes (SOD, GST, and CAT), as well as impaired nutrient metabolism (alpha-amylase). Given their antibacterial property, CuO and ZnO NPs decreased species richness and diversity of the gut bacterial community and shifted their configuration to overt microbiome i.e., decreased abundance of probiotics (e.g., Acetobacter) and increased pathobionts (e.g., Pseudomonas, Bacillus, Escherichia, Enterococcus, Ralstonia, etc.) proportions. Overall, this integrated study revealed the unintended negative effects of CuO and ZnO NPs on silkworms and highlighted the potential to inevitably affect all living things due to intensive and possible mishandling of nanomaterials., 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.)

The potential of combination therapy using nanoparticle delivery systems in improving triple-negative breast cancer treatment efficacy remains to be explored. Here, we report a novel nanoparticle system using a cholesterol biguanide conjugate hydrochloride (CBH) as both a drug and carrier to load magnolol (MAG). Poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) and aminoethyl anisamide-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (AEAA-PEG-PLGA) were added to form nanoparticles. Nanoparticles accumulated most in tumor tissues when the weight ratio of AEAA-PEG-PLGA to mPEG-PLGA was 4:1. MAG and CBH exerted a synergistic inhibitory effect on 4 T1 cells. An in vitro study showed that nanoparticles displayed the highest tumor cell uptake rate, highest apoptosis rate, and strongest inhibitory effect on tumor cell migration and monoclonal formation. CBH might promote nanoparticle uptake by cells and lysosomal escape. After intravenous administration to mice with 4 T1 breast tumors in situ, the nanoparticles inhibited tumor growth without obvious toxicity. Western blot results showed that nanoparticles altered the levels of p53, p-AKT, and p-AMPK in the tumor tissue. Moreover, cell apoptosis was found in the same area of H&E-stained and TUNEL-stained tumors treated with the nanoparticles. Collectively, this nanoparticle system provides a novel combination drug delivery strategy for treating triple-negative breast cancer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Direct delivery of drugs into the nucleus is a promising nanotechnology therapy, since the nucleus is one of the most important organelles controlling cell proliferation and apoptosis. Here, we report a nucleus-targeting nanocarrier for nuclear drug delivery using a pH/enzyme dual sensitive strategy. The specific ligand PGM (PKKKRKV-GFLG-Mp), composed of nuclear localization sequence (PKKKRKV), enzyme-sensitive tetrapeptide (Gly-Phe-Leu-Gly, GFLG), and pH-sensitive molecules morpholine (Mp), was modified on poly (amidoamine) (PAMAM) by maleimide active polyethylene glycol ester (NHS-PEG-MAL) to form PAMAM-PEG-PGM. Doxorubicin (DOX) was loaded into the cavity of PAMAM to prepare DOX/PAMAM-PEG-PGM. In vitro release study suggested DOX release from DOX/PAMAM-PEG-PGM nanoparticles followed pH and enzyme-triggered manner. In vitro studies showed DOX/PAMAM-PEG-PGM nanoparticles could not only promote cell internalization through the charge switching of morpholine, but also achieve nuclear internalization by the mediation of composite formed by NLS and importin α/β receptor. Further, employing H22 tumour-bearing BALB/c mice as a model, the systemic distribution and anticancer effects of nanoparticles were studied in vivo . The results indicated the nanoparticles could preferentially accumulate in the tumour site in vivo , and the tumour inhibition rate was 88.47%. In short, the nanoparticles developed could be promising in application to nucleus-targeting therapy to enhance antitumour activity.

Lanthanide-doped upconversion nanoparticles (UCNPs), characterized by converting low-energy excitation to high-energy emission, have attracted considerable interest due to their inherent advantages of large anti-Stokes shifts, sharp and narrow multicolor emissions, negligible autofluorescence background interference, and excellent chemical- and photo-stability. These features make them promising luminophores for sensing applications. In this review, we give a comprehensive overview of lanthanide-doped upconversion nanophosphors including the fundamental principle for the construction of UCNPs with efficient upconversion luminescence (UCL), followed by state-of-the-art strategies for the synthesis and surface modification of UCNPs, and finally describing current advances in the sensing application of upconversion-based probes for the quantitative analysis of various analytes including pH, ions, molecules, bacteria, reactive species, temperature, and pressure. In addition, emerging sensing applications like photodetection, velocimetry, electromagnetic field, and voltage sensing are highlighted., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, a chitosan-based, self-assembled nanosystem that codelivered microRNA34a (miR34a) and doxorubicin (Dox) with hyaluronic acid (HA) modification (named CCmDH NPs) was developed to reverse the resistance of breast cancer (BCa) cells to Dox. The CCmDH NPs had a diameter of 180 ± 8.3 nm and a ζ potential of 16.5 mV with a slow-release effect for 96 h. The codelivery system could protect miR34a from nuclease and serum degradation and transport miR34a and Dox into drug-resistant MCF-7/A cells. In addition, the CCmDH NPs could inhibit proliferation and promote apoptosis by regulating the protein expression of B-cell lymphoma-2 (Bcl-2) and poly(ADP-ribose) polymerase (PARP) and inhibit invasion, metastasis, and adhesion by regulating E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. The CCmDH NPs induced a 73.7% tumor reduction in xenograft tumor growth in nude mice in vivo . This study provides evidence for the anticancer activity of CCmDH NPs carrying Dox and miR34a in BCa, especially metastatic Dox-resistant BCa models.

A new electrochemical sensor has been constructed for ultra-sensitive detection of lead ions (Pb 2+ ) by square wave anodic stripping voltammetry (SWASV), based on the copper sulfide/graphitic carbon nitride nanocomposite modified glassy carbon electrode (CuS/g-C 3 N 4 /GCE). First, spherical CuS nanoparticles with good electrical conductivity were anchored on layered g-C 3 N 4 with high coordination activity, affording an excellent electrode modifier CuS/g-C 3 N 4 nanocomposite. Then, the performance of the CuS/g-C 3 N 4 /GCE and its electrochemical response to Pb 2+ were thoroughly studied, and the sensing mechanism was investigated. On the one hand, the CuS/g-C 3 N 4 nanocomposite has greatly improved the electron transportation and electrode performance through functional complementarity - CuS endows g-C 3 N 4 with a good electrical conductivity and a large active specific surface area, while g-C 3 N 4 endows CuS with high dispersibility and strong adsorption. On the other hand, the CuS/g-C 3 N 4 modifier has effectively promoted the deposition of trace Pb 2+ from the solution onto the electrode surface by means of synergistic enrichment (crucial for amplification of detection signals) - g-C 3 N 4 can coordinate with Pb 2+ by its large number of conjugated triazine heterocyclic rings in its molecular framework, while CuS can adsorb Pb 2+ due to its inherent size effect of nanomaterials. The proposed sensor can efficiently detect Pb 2+ in the concentration range of 0.050-5.000 μM with a limit of detection (LOD) as low as 4.00 nM, and can be well applied for the detection of trace Pb 2+ in actual tea samples.

The integration of hypoxia-activated chemotherapy with photodynamic therapy (PDT) has newly become a potent strategy for tumor treatment. Herein, a reactive oxygen species (ROS)-responsive drug carriers (PS@AQ4N/mPEG-b-PSe NPs) are fabricated based on the amphiphilic selenium-containing methoxy poly(ethylene glycol)-polycarbonate (mPEG-b-PSe), the hydrophobic photosensitizer (PS), and hypoxia-activated prodrug Banoxantrone (AQ4N). The obtained nanoparticles are spherical with an average diameter of 100 nm as characterized by transmission electron microscope (TEM) and dynamic laser scattering (DLS) respectively. The encapsulation efficiency of the PS and AQ4N reaches 92.83% and 51.04% at different conditions, respectively, by UV-vis spectrophotometer. It is found that the drug release is accelerated due to the good ROS responsiveness of mPEG-b-PSe and the cumulative release of AQ4N is up to 89% within 30 h. The cell test demonstrates that the nanoparticles dissociate when triggered by the ROS stimuli in the cancer cells, thus the PS is exposed to more oxygen and the ROS generation efficiency is enhanced accordingly. The consumption of oxygen during PDT leads to the increased tumor hypoxia, and subsequently activates AQ4N into cytotoxic counterpart to inhibit tumor growth. Therefore, the synergistic therapeutic efficacy demonstrates this drug delivery has great potential for antitumor therapy., (© 2021 Wiley-VCH GmbH.)

GSH-mediated liver biotransformation is a crucial physiological process demanding efficient research tools. Here, we report a type of amorphous Fe x Mn y O nanoparticles (AFMO-ZDS NPs) as redox-activated probes for in vivo visualization of the dynamics of GSH-mediated biotransformation in liver with T 1 -weighted magnetic resonance imaging (MRI). This imaging technique reveals the periodic variations in GSH concentration during the degradation of AFMO-ZDS NPs due to the limited transportation capacity of GSH carriers in the course of GSH efflux from hepatocytes to perisinusoidal space, providing direct imaging evidence for this important carrier-mediated process during GSH-mediated biotransformation. Therefore, this technique offers an effective method for in-depth investigations of GSH-related biological processes in liver under various conditions as well as a feasible means for the real-time assessment of liver functions, which is highly desirable for early diagnosis of liver diseases and prompt a toxicity evaluation of pharmaceuticals.

Tuberculosis (TB) is major health concern and reason of deaths from decades to current date. Even though with a lot of advancements, diagnostic techniques, and discovery of standard antibiotics TB remains crucial challenge and can create worst scenario for human health in near future. Nanoparticles play emerging role in diagnosis and treatment of TB. In this study, we developed mesoporous silica nanoparticles containing gold (MSNs@GNPs) for rapid diagnosis and treatment of TB. The physicochemical characterization revealed effective surface morphology and particles diameter, that is applicable for in vitro applications. The in vitro antimicrobial analysis revealed that the designed MSNs@GNPs has retained significantly lower minimal inhibitory concentration (MIC) values and can effectively demolish mycobacterium tuberculosis (Mtb). Furthermore, the diagnosis efficiency of the MSNs@GNPs was evaluated by calorimetric analysis. Which demonstrates that MSNs@GNPs can be used for rapid diagnosis of the tuberculosis when applied on in vitro culture of the Mtb. The current study needs further verification on human's clinical samples from tuberculosis patients. However, MSNs@GNPs can be a versatile clinical approach for the rapid diagnosis and clinical treatment of the tuberculosis., (© 2021. The Author(s).)

RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown of pathological genes, expression of therapeutic proteins, and programmed gene editing. Due to the inherent instability and negative-charges of RNA molecules, RNA-based therapeutics can make the most use of delivery systems to overcome biological barriers and to release the RNA payload into the cytosol. Among different types of delivery systems, lipid-based RNA delivery systems, particularly lipid nanoparticles (LNPs), have been extensively studied due to their unique properties, such as simple chemical synthesis of lipid components, scalable manufacturing processes of LNPs, and wide packaging capability. LNPs represent the most widely used delivery systems for RNA-based therapeutics, as evidenced by the clinical approvals of three LNP-RNA formulations, patisiran, BNT162b2, and mRNA-1273. This review covers recent advances of lipids, lipid derivatives, and lipid-derived macromolecules used in RNA delivery over the past several decades. We focus mainly on their chemical structures, synthetic routes, characterization, formulation methods, and structure-activity relationships. We also briefly describe the current status of representative preclinical studies and clinical trials and highlight future opportunities and challenges.