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The challenge remains in developing hemostatic dressings that can fulfill both hemostatic and repair functions to meet clinical demands worldwide. Herein, the biodegradable powders composed of benzeneboronic acid-modified sodium alginate/catechol-modified quaternized chitosan hydrogel (SBQCC) networks and bioactive cerium oxide nanoparticles (CNPs), were prepared for hemostasis and promoting wound healing. The SBQCC/CNPs powders had good self-gelation ability, water absorption ratio, tissue adhesiveness and biocompatibility. The SBQCC/CNPs powders could not only rapidly absorb a large amount of blood to concentrate coagulation factors when applied on bleeding wounds, but also formed an adhesive hydrogel physical barrier to control bleeding in situ. Meanwhile, the aggregation and activation of red blood cells and platelets induced by the SBQCC/CNPs powders can initiate the forming of internal blood clot with fibrin to further enhance the hemostatic effect. The SBQCC/CNPs powders demonstrated excellent hemostatic performance in non-compressible rat tail vein bleeding and rabbit liver bleeding models. In addition, SBQCC/CNPs powder-derived hydrogels had antibacterial activity and multiple biological activities, including antioxidant, anti-inflammatory and promoting angiogenesis for accelerating wound healing. Therefore, the SBQCC/CNPs powders can accelerate wound healing while achieving effective hemostasis, which will be a promising hemostatic dressing., 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.)

Hepatocellular injury, a pivotal contributor to liver diseases, particularly hepatitis, lacks effective pharmacological treatments. Interleukin-22 (IL-22), crucial for liver cell survival, shows potential in treating liver diseases by regulating repair and regeneration through signal transducer and activator of transcription 3 (STAT3) activation. However, the short half-life and off-target effects limit its clinical applications. To address these issues, lipid nanoparticles are employed to deliver synthetic IL-22 mRNA (IL-22/NP) for in situ IL-22 expression in hepatocytes. The study reveals that IL-22/NP exhibits liver-targeted IL-22 expression, with increased IL-22 levels detected in the liver as early as 3 h postintravenous injection, lasting up to 96 h. Furthermore, IL-22/NP activates STAT3 signaling in an autocrine or paracrine manner to upregulate downstream factors Bcl-xL and CyclinD1, inhibiting hepatocyte apoptosis and promoting cell proliferation. The therapeutic efficacy of IL-22/NP is demonstrated in both chronic and acute liver injury models, suggesting IL-22 mRNA delivery as a promising treatment strategy for hepatitis and liver diseases involving hepatocellular injury., (© 2024 Wiley‐VCH GmbH.)

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and has many characteristics including high metastatic rates, poor overall survival, and low response to traditional chemotherapy. Photodynamic therapy (PDT), emerging as a precise treatment modality, has shown promise in improving the antitumor response. However, it still faces challenges such as limited light penetration depth, rapid oxygen consumption, and inadequate targeting ability. In this study, we developed Rose Bengal (RB, photosensitizer) and oxygen co-loaded CREKA-modified UCNP-based nanoliposomes (CLIP-RB-PFOB@UCNP) for tumor targeting and near-infrared (NIR)-triggered deep and long-lasting PDT. Our results demonstrated that CLIP-RB-PFOB@UCNP effectively targeted and accumulated in tumor tissue through the interaction between CREKA and fibronectin, which is overexpressed in tumor cells. Under NIR irradiation, CLIP-RB-PFOB@UCNP exhibited significant destruction of orthotopic tumors, reduced the level of HIF-1α, and efficiently suppressed lung metastasis in a metastatic TNBC model. In conclusion, this study offers new avenues for improving the therapeutic outcomes of PDT for clinical TNBC treatment.

Endoscopic tattooing is a localization technique that is particularly important for identifying gastrointestinal lesions for follow-up and subsequent treatment. However, the dyes currently used for endoscopic tattooing have a short tattooing time, high cost, and many side effects. Herein, we designed and prepared polydopamine (PDA) nanoparticles modified with polyvinylpyrrolidone (PVP) for endoscopic tattooing using a physical encapsulation method. PDA has good stability and high adhesion properties, and its stability was further enhanced after PVP modification. In vitro and in vivo tests demonstrated that PDA/PVP has good biosafety. Endoscopic tattooing with PDA/PVP in a porcine model showed that the dye could be stabilized in the digestive tract for at least 60 days. Furthermore, our research results demonstrated that PDA/PVP has excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging ability and can promote wound healing. Overall, the strategy proposed herein will lead to the use of an innovative dye for endoscopic tattooing of gastrointestinal lesions.

As artificial receptors for protein recognition, epitope-imprinted polymers combined with fluorescence sensing based on quantum dots (QDs) can be potentially used for biological analysis and disease diagnosis. However, the usual way for fabrication of QD sensors through unoriented epitope imprinting is confronted with the problems of disordered imprinting sites and low template utilization. In this context, a facile and efficient oriented epitope surface imprinting was put forward based on immobilization of the epitope templates via thiol-disulfide exchange reactions. With N-succinimidyl 3-(2-pyridyldithio)-propionate (SPDP) as a heterobifunctional reagent, cysteine-modified epitopes of cytochrome c were anchored on the surface of pyridyl disulfide functionalized silica nanoparticles sandwiching CdTe QDs. After surface imprinting via a sol-gel process, the epitope templates were removed from the surface-imprinted layers simply by reduction of the thiol-disulfide, affording oriented epitope-imprinted sites. By this method, the amount of epitope templates was only 1/20 of traditionally unoriented epitopes. The resulting sensors demonstrated significantly enhanced imprinting performance and high sensitivity, with the imprinting factor increasing from 2.6 to 3.9, and the limit of detection being 91 nM. Such epitope-oriented surface-imprinted method may offer a new design strategy for the construction of high-affinity protein recognition nanomaterials with fluorescence sensing., 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: Hemorrhagic shock was a leading cause of death worldwide, with myocardial injury being a primary affected organ. As commonly used solutions in fluid resuscitation, acetated Ringer's (AR) and Lactate Ringer's solution (LR) were far from perfect for their adverse reactions such as lactic acidosis and electrolyte imbalances. In previous studies, TPP@PAMAM-MR (TPP-MR), a novel nanocrystal resuscitation fluid has been found to protect against myocardial injury in septic rats. However, its role in myocardial injury in rats with hemorrhagic shock and underlying mechanism is unclear., Methods: The hemorrhagic shock rats and hypoxia-treated cardiomyocytes (H9C2) were utilized to investigate the impact of TPP-MR on cardiac function, mitochondrial function, and lipid peroxidation. The expressions of ferritin-related proteins glutathione peroxidase 4 (GPX4), Acyl CoA Synthase Long Chain Family Member 4 (ACSL4), and Cyclooxygenase-2(COX2) were analyzed through Western blotting to explore the mechanism of TPP-MR on hemorrhagic myocardial injury., Results: TPP-MR, a novel nanocrystalline resuscitation fluid, was synthesized using TPP@PAMAM@MA as a substitute for L-malic acid. We found that TPP-MR resuscitation significantly reduced myocardial injury reflected by enhancing cardiac output, elevating mean arterial pressure (MAP), and improving perfusion. Moreover, TPP-MR substantially prolonged hemorrhagic shock rats' survival time and survival rate. Further investigations indicated that TPP-MR improved the mitochondrial function of myocardial cells, mitigated the production of oxidative stress agents (ROS) and increased the glutathione (GSH) content. Additionally, TPP-MR inhibited the expression of the ferroptosis-associated GPX4 protein, ACSL4 and COX2, thereby enhancing the antioxidant capacity., Conclusion: The results showed that TPP-MR had a protective effect on myocardial injury in rats with hemorrhagic shock, and its mechanism might be related to improving the mitochondrial function of myocardial cells and inhibiting the process of ferroptosis., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Tan et al.)

As the drawbacks of antibiotics in treating bacterial infections emerged, physical methods such as near-infrared-activated (NIR-activated) bacterial killing, have attracted great interests for their advantages of no resistance, short action time and few side effects. In this manuscript, NIR-activated bacteria-killing performance of chiral copper sulphide nanoparticles (L-/d-CuS NPs) was investigated using linearly polarized light (LPL) and circularly polarized light (CPL) as illumination sources, respectively. Chiral CuS NPs showed enhanced NIR-activated bacteria-killing effect compared with achiral CuS NPs under the same conditions. Moreover, these chiral CuS NPs showed obvious chirality-related antibacterial effect: the bacterial killing was more efficient under CPL activation, and L- and d-CuS NPs had higher antibacterial efficiency under left circularly polarized light (LCPL) and right circularly polarized light (RCPL), respectively. The possible mechanism of bacteria-killing performance for chiral CuS NPs was discussed in detailed. Photothermal bacteria-killing tests of chiral CuS NPs "sealed" in polydimethylsiloxane (PDMS) demonstrated the individual influence of photothermal effect. These observations in this paper could provide ideas for the potential applications of chiral nanostructures with enhanced photothermal effect in efficient bacterial killing., 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.)

Cesium lead halide (CsPbX 3 , X = Br, Cl, and I) nanocrystals (NCs) are widely concerned and applied in many fields due to the excellent photoelectric performance. However, the toxicity of Pb and the loss of luminescence in water limit its application in vivo. A stable perovskite nanomaterial with good bioimaging properties is developed by incorporating europium (Eu) in CsPbX 3 NCs followed with the surface coating of silica (SiO 2 ) shell (CsPbX 3 :Eu@SiO 2 ). Through the surface coating of SiO 2 , the luminescence stability of CsPbBr 3 in water is improved and the leakage of Pb 2+ is significantly reduced. In particular, Eu doping inhibits the photoluminescence quantum yield reduction of CsPbBr 3 caused by SiO 2 coating, and further reduces the release of Pb 2+ . CsPbBr 3 :Eu@SiO 2 nanoparticles (NPs) show efficient luminescence in water and good biocompatibility to achieve cell imaging. More importantly, CsPb(ClBr) 3 :Eu@SiO 2 NPs are obtained by adjusting the halogen components, and green light and blue light are realized in zebrafish imaging, showing good imaging effect and biosafety. The work provides a strategy for advanced perovskite nanomaterials toward biological practical application., (© 2024 Wiley‐VCH GmbH.)

The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4 + and CD8 + T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF)., 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.)

Fenton chemistry-mediated antimicrobials have demonstrated great promise in antibacterial therapy. However, the short life span and diffusion distance of hydroxyl radicals dampen the therapeutic efficiency of these antimicrobials. Herein, inspired by the neutrophil extracellular trap (NET), in which bacteria are trapped and agglutinated via electronic interactions and killed by reactive oxygen species, we fabricated a NET-mimic nanoparticle to suppress bacterial infection in a "trap & kill" manner. Specifically, this NET-mimic nanoparticle was synthesized via polymerization of ferrocene monomers followed by quaternization with a mannose derivative. Similar to the NET, the NET-mimic nanoparticles trap bacteria through electronic and sugar-lectin interactions between their mannose moieties and the lectins of bacteria, forming bacterial agglutinations. Therefore, they confine the spread of the bacteria and restrict the bacterial cells to the destruction range of hydroxyl radicals. Meanwhile, the ferrocene component of the nanoparticle catalyzes the production of highly toxic hydroxyl radicals at the H 2 O 2 rich infection foci and effectively eradicates the agglutinated bacteria. In a mouse model of an antimicrobial-resistant bacteria-infected wound, the NET-mimic nanoparticles displayed potent antibacterial activity and accelerated wound healing.

The diseases caused by foodborne pathogens have a serious impact on human health and social stability. Conventional detection methods can involve long assay times and complex pretreatment steps, making them unsuitable for rapid, large-scale analysis of food samples. We constructed a novel nano-fluorescence sandwich immunosorbent immunoassay (nano-FSIA) to rapidly detect Salmonella Typhimurium in food, based on strong covalent binding between streptavidin and biotin. We used antibodies coupled to large particle-size fluorescent microspheres as fluorescent probes for direct quantitative analysis of S. typhimurium in milk. The optimized parameters were determined, and specificity and sensitivity were validated in phosphate-buffered saline (PBS) and milk. The results demonstrated a wide dynamic detection range for S. typhimurium (10 3 -10 8 colony forming units [CFU]/mL), with the limit of detection in PBS and milk at 234 and 346 CFU/mL, respectively. The results of nano-FSIA were consistent with those of plate counts and enzyme-linked immunosorbent assays, providing an effective and promising single-bacterium counting method for the rapid detection of Salmonella., 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 B.V.)

In the context of bone regeneration, nanoparticles harboring osteogenic factors have emerged as pivotal agents for modulating the differentiation fate of stem cells. However, persistent challenges surrounding biocompatibility, loading efficiency, and precise targeting ability warrant innovative solution. In this study, a novel nanoparticle platform founded upon the zeolitic imidazolate framework-8 (ZIF-8) is introduced. This new design, CDC20@ZIF-8@eM-Apt, involves the envelopment of ZIF-8 within an erythrocyte membrane (eM) cloak, and is coupled with a targeting aptamer. ZIF-8, distinguished by its porosity, biocompatibility, and robust cargo transport capabilities, constitutes the core framework. Cell division cycle protein 20 homolog (CDC20) is illuminated as a new target in bone regeneration. The eM plays a dual role in maintaining nanoparticle stability and facilitating fusion with target cell membranes, while the aptamer orchestrates the specific recruitment of bone marrow mesenchymal stem cells (BMSCs) within bone defect sites. Significantly, CDC20@ZIF-8@eM-Apt amplifies osteogenic differentiation of BMSCs via the inhibition of NF-κB p65, and concurrently catalyzes bone regeneration in two bone defect models. Consequently, CDC20@ZIF-8@eM-Apt introduces a pioneering strategy for tackling bone defects and associated maladies, opening novel avenues in therapeutic intervention., (© 2023 Wiley-VCH GmbH.)

Nanodrug delivery systems based on tumor microenvironment responses have shown excellent performance in tumor-targeted therapy, given their unique targeting and drug-release characteristics. Matrix metalloproteinases (MMPs) have been widely explored owing to their high specificity and expression in various tumor microenvironments. The design of an enzyme-sensitive nanodelivery system using MMPs as targeted receptors could markedly improve the performance of drug targeting. The current review focuses on the development and application of MMP-responsive drug carriers, and summarizes the classification of single- and multi-target nanocarriers based on their MMP responsiveness. The potential applications and challenges of this nanodrug delivery system are discussed to provide a reference for designing high-performance nanodrug delivery systems., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A brain-targeting nanodelivery system has been a hot topic and has undergone rapid progression. However, due to various obstacles such as the intestinal epithelial barrier (IEB) and the blood-brain barrier (BBB), few nanocarriers can achieve brain-targeting through oral administration. Herein, an intelligent oral brain-targeting nanoparticle (FTY@Man NP) constructed from a PLGA-PEG skeleton loaded with fingolimod (FTY) and externally modified with mannose was designed in combination with a glucose control strategy for the multitarget treatment of Alzheimer's disease (AD). The hydrophilic and electronegative properties of the nanoparticle facilitated its facile penetration through the mucus barrier, while the mannose ligand conferred IEB targeting abilities to the nanoparticle. Subsequently, glycemic control allowed the mannose-integrated nanoparticle to hitchhike the glucose transporter 1 (GLUT1) circulation across the BBB. Finally, the released FTY modulated the polarity of microglia from pro-inflammatory M1 to anti-inflammatory M2 and normalized the activated astrocyte, enhancing the clearance of toxic protein Amyloid-β (Aβ) while alleviating oxidative stress and neuroinflammation. Notably, both in vitro and in vivo results have consistently demonstrated that the oral administration of FTY@Man NP could effectively traverse the multiple barriers, thereby exerting significant therapeutic effects. This breakthrough holds the promise of realizing a highly effective orally administered treatment for AD.

T-cell exhaustion refers to a state of T-cell dysfunction commonly observed in chronic infections and cancer. Immune checkpoint molecules blockading using PD-1 and TIM-3 antibodies have shown promising results in reversing exhaustion, but this approach has several limitations. The treatment of T-cell exhaustion is still facing great challenges, making it imperative to explore new therapeutic strategies. With the development of nanotechnology, nanoparticles have successfully been applied as drug carriers and delivery systems in the treatment of cancer and infectious diseases. Furthermore, nanoparticle-based immunotherapy has emerged as a crucial approach to reverse exhaustion. Here, we have compiled the latest advances in T-cell exhaustion, with a particular focus on the characteristics of exhaustion that can be targeted. Additionally, the emerging nanoparticle-based delivery systems were also reviewed. Moreover, we have discussed, in detail, nanoparticle-based immunotherapies that aim to reverse exhaustion, including targeting immune checkpoint blockades, remodeling the tumor microenvironment, and targeting the metabolism of exhausted T cells, etc. These data could aid in comprehending the immunopathogenesis of exhaustion and accomplishing the objective of preventing and treating chronic diseases or cancer.

Purpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe 3 O 4 @ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC., Methods: Firstly, we synthesized and characterized SP94-Fe 3 O 4 @ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety., Results: SP94-Fe 3 O 4 @ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm 2 ) and a set concentration (50 µg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells., Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study., (© 2024 Jin et al.)

Nano drug delivery systems offer several benefits, including enhancing drug solubility, regulating drug release, prolonging drug circulation time, and minimized toxicity and side effects. However, upon entering the bloodstream, nanoparticles (NPs) encounter a complex biological environment and get absorbed by various biological components, primarily proteins, leading to the formation of a 'Protein Corona'. The formation of the protein corona is affected by the characteristics of NPs, the physiological environment, and experimental design, which in turn affects of the immunotoxicity, specific recognition, cell uptake, and drug release of NPs. To improve the abundance of a specific protein on NPs, researchers have explored pre-coating, modifying, or wrapping NPs with the cell membrane to reduce protein adsorption. This paper, we have reviewed studies of the protein corona in recent years, summarized the formation and detection methods of the protein corona, the effect of the protein corona composition on the fate of NPs, and the design of new drug delivery systems based on the optimization of protein corona to provide a reference for further study of the protein corona and a theoretical basis for the clinical transformation of NPs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In recent years, PbO 2 electrodes have received widespread attention due to their high oxygen evolution reaction (OER) activity. However, due to the brittle nature of the plating layer, it is easy to cause the active layer to fall off. Pb 2+ will leach out with the electrochemical process causing secondary pollution. The starting point of this study is established to improve the stability and adhesion of the electrode coating. Electrochemical oxidation technology has the characteristics of high treatment efficiency, wide range of applications, and non-polluting environment. In this study, conventional PbO 2 electrodes were modified by using co-deposition of ZrO 2 nanoparticles. In addition, α-PbO 2 was added to increase the stability of the electrodes. At a high current density of 1 A/cm 2 , the accelerated life of the pure PbO 2 electrode is 648 h, the accelerated life of the PbO 2 -ZrO 2 electrode is 1.37 times that of the pure PbO 2 , and the electrode with an added α-PbO 2 layer is 1.69 times that of the pure PbO 2 electrode. The amount of dissolved Pb 2+ was only 29% of that of pure PbO 2 . The electrochemical performance of the electrode is evaluated by studying the degradation effect of ceftriaxone sodium (CXM). The addition of ZrO 2 nanoparticles alters the particle size and deposition content of PbO 2 , leading to a unique crystal structure distinct from pure PbO 2 . Compared to conventional PbO 2 electrodes, the PbO 2 -ZrO 2 can remove chemical oxygen demand (COD) and pollutants more efficiently, removing for 59% increased by 38.47%. Therefore, PbO 2 -ZrO 2 is of great value in the field of electrochemical degradation of industrial pollutants., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Candida albicans ( C. albicans ) forms pathogenic biofilms, and the dense mucus layer secreted by the epithelium is a major barrier to the traditional antibiotic treatment of mucosa-associated C. albicans infections. Herein, we report a novel anti-biofilm strategy of mucus-permeable sonodynamic therapy (mp-SDT) based on ultrasound (US)-mediated amphotericin B-loaded PEGylated PLGA nanoparticles (AmB-NPs) to overcome mucus barrier and enable the eradication of C. albicans biofilm., Methods: AmB-NPs were fabricated using ultrasonic double emulsion method, and their physicochemical and sonodynamic properties were determined. The mucus and biofilm permeability of US-mediated AmB-NPs were further investigated. Moreover, the anti-biofilm effect of US-mediated AmB-NPs treatment was thoroughly evaluated on mucus barrier abiotic biofilm, epithelium-associated biotic biofilm, and C. albicans- induced rabbit vaginal biofilms model. In addition, the ultrastructure and secreted cytokines of epithelial cells and the polarization of macrophages were analyzed to investigate the regulation of local cellular immune function by US-mediated AmB-NPs treatment., Results: Polymeric AmB-NPs display excellent sonodynamic performance with massive singlet oxygen ( 1 O 2 ) generation. US-mediated AmB-NPs could rapidly transport through mucus and promote permeability in biofilms, which exhibited excellent eradicating ability to C. albicans biofilms. Furthermore, in the vaginal epithelial cells (VECs)-associated C. albicans biofilm model, the mp-SDT scheme showed the strongest biofilm eradication effect, with up to 98% biofilm re-formation inhibition rate, improved the ultrastructural damage, promoted local immune defense enhancement of VECs, and regulated the polarization of macrophages to the M1 phenotype to enhance macrophage-associated antifungal immune responses. In addition, mp-SDT treatment exhibited excellent therapeutic efficacy against C. albicans- induced rabbit vaginitis, promoted the recovery of mucosal epithelial ultrastructure, and contributed to the reshaping of a healthier vaginal microbiome., Conclusion: The synergistic anti-biofilm strategies of mp-SDT effectively eradicated C. albicans biofilm and simultaneously regulated local antifungal immunity enhancement, which may provide a new approach to treat refractory drug-resistant biofilm-associated mucosal candidiasis., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Yang et al.)

This study addresses the limitations of konjac glucomannan (KGM) films in mechanical properties, hydrophobicity and antibacterial activities. For the first time, a zein-pectin nanoparticle-stabilized corn germ oil-oregano essential oil Pickering emulsion (ZPCEO) was incorporated into KGM, with the resulting film being further ionically crosslinked with Ca 2+ , Cu 2+ or Fe 3+ . FTIR, SEM and EDS results showed that the metal ions were crosslinked with the hydroxyl and carbonyl groups of polysaccharides and uniformly distributed throughout the films (degree of crosslinking: Fe 3+ > Cu 2+ > Ca 2+ ). Compared with pure KGM films, the ionic crosslinked ZPCEO/KGM (IL-ZPCEO/KGM) films have superior water resistance mechanical properties, and exhibit unique UV-blocking properties, antioxidant and antibacterial activities. The ZPCEO/KGM-Fe 3+ film offered the best all-round properties, including the highest tensile strength, water resistance, UV-blocking capacity, and antimicrobial activity. Thus, ionic crosslinking of ZPCEO/KGM films can be applied to the preparation of food packaging for use in high humidity environments., 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.)

Despite the wide range of applications of bright NIR-II polymethine scaffolds in biomedical imaging, their solvatochromism and aggregation-caused quenching (ACQ) effects in aqueous solutions limit their inherent brightness using traditional encapsulation methods, and effective hydrophilization strategies are still scarce. Here, a new set of Flav dyes is synthesized and PEGylated, followed by manufacturing DSPE@FlavP 2000 nanoparticles using a self-adaptive co-assembly strategy to overcome these limitations. FlavP 2000 can autonomously adjust its conformation when co-assembled with DSPE-PEG 2000 , resulting in high-efficiency luminescence (≈44.9% fluorescence of Flav in DMSO). DSPE@FlavP 2000 enables NIR-IIb (>1500 nm) angiography with high signal-to-noise ratios. Notably, this co-assembly can occur in situ between FlavP 2000 with proteins in the living body based on a novel mechanism of brightness activation induced by disassembly (BAD), achieving consistent brightness as DSPE@FlavP 2000 in blood or serum. The self-adaptive co-assembly strategy can be enhanced by incorporating an IPA moiety, which dynamically binds to albumin to prolong the dye's blood circulation time. Thus, the "enhanced" BAD is successfully applied to long-term vascular imaging and sciatic nerve imaging. Both the self-adaptive co-assembly strategy and BAD phenomenon improve the selectivity and availability of the hydrophilization methods, paving the way for efficient biological applications of polymethine dyes., (© 2023 Wiley-VCH GmbH.)

Disease or organ damage due to unhealthy living habits, or accidents, is inevitable. Discovering an efficient strategy to address these problems is urgently needed in the clinic. In recent years, the biological applications of nanotechnology have received extensive attention. Among them, as a widely used rare earth oxide, cerium oxide (CeO 2 ) has shown good application prospects in biomedical fields due to its attractive physical and chemical properties. Here, the enzyme-like mechanism of CeO 2 is elucidated, and the latest research progress in the biomedical field is reviewed. At the nanoscale, Ce ions in CeO 2 can be reversibly converted between +3 and +4. The conversion process is accompanied by the generation and elimination of oxygen vacancies, which give CeO 2 the performance of dual redox properties. This property facilitates nano-CeO 2 to catalyze the scavenging of excess free radicals in organisms, hence providing a possibility for the treatment of oxidative stress diseases such as diabetic foot, arthritis, degenerative neurological diseases, and cancer. In addition, relying on its excellent catalytic properties, customizable life-signaling factor detectors based on electrochemical techniques are developed. At the end of this review, an outlook on the opportunities and challenges of CeO 2 in various fields is provided., (© 2023 Wiley-VCH GmbH.)

Invasive glioma usually disrupts the integrity of the blood-brain barrier (BBB), making the delivery of nanodrugs across the BBB possible, but sufficient targeting ability is still avidly needed to improve drug accumulation in glioma. Membrane-bound heat shock protein 70 (Hsp70) is expressed on the membrane of glioma cells rather than adjacent normal cells, therefore it can serve as a specific glioma target. Meanwhile, prolonging the retention in tumors is important for active-targeting nanoparticles to overcome receptor-binding barriers. Herein, the Hsp70-targeting and acid-triggered self-assembled gold nanoparticles (D-A-DA/TPP) are proposed to realize selective delivery of doxorubicin (DOX) to glioma. In the weakly acidic glioma matrix, D-A-DA/TPP formed aggregates to prolong retention, improve receptor-binding efficiency and facilitate acid-responsive DOX release. DOX accumulation in glioma induced immunogenic cell death (ICD) to promote antigen presentation. Meanwhile, combination with the PD-1 checkpoint blockade further activate T cells and provokes robust anti-tumor immunity. The results showed that D-A-DA/TPP can induce more glioma apoptosis. Furthermore, in vivo studies indicated D-A-DA/TPP plus PD-1 checkpoint blockade significantly improved median survival time. This study offeres a potential nanocarrier combining size-tunable strategy with active targeting ability to increase drug enrichment in glioma and synergizes with PD-1 checkpoint blockade to achieve chemo-immunotherapy., (© 2023 Wiley-VCH GmbH.)

The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength. Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e., signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

As a biomarker of hepatocellular carcinoma (HCC) biopsy, circulating tumor cells (CTCs) are often used in the diagnosis of cancer and treatment guidance. For CTCs detection, immuno-magnetic nanoparticles (IMNs) are one of the most commonly used platforms. However, the nonspecific adsorption of proteins and non-tumor cells weakens the performance of IMNs to capture CTCs. In this work, we developed an IMNs platform which was constructed by a biomimetic protein corona precoating and a polyethylene glycol (PEG) spacer to form the PEG and corona-coated IMNs (IP-CMNs). Due to the dual stealth effect of protein corona precoating and PEG spacer, the nonspecific protein adsorption and cell binding of P-CMNs could reduce by ∼5.5- and ∼5.4-fold, respectively, compared with those of unmodified particles. Furthermore, the PEG spacer could not only reduce the interaction between IP-CMNs and leukocytes but also enhance the capture performance toward tumor cells. By using artificial blood samples, the capture efficiency of IP-CMNs toward rare CTCs was found to be 88.3%, while it was 70.5% by using commercial IMNs. Finally, CTCs were successfully isolated in all HCC patient blood samples (7/7) using IP-CMNs. These results provide insight into the use of the multifunctional nanoplatform as a useful tool for CTCs detection.

A novel chiral molecularly imprinted polymer TiO 2 nanoparticle was synthesized in one step for the enantioseparation of phenylalanine in coated capillary electrochromatography. To the author's knowledge, the chiral molecularly imprinted nanomaterials have still not been reported, to date. Chiral molecularly imprinted TiO 2 nanomaterials (L-PHE@MIP(APTES-TEOS)@TiO 2 ) were used as a chiral stationary phase to separate the phenylalanine enantiomers in coated capillary electrochromatography (CEC). The imprinted coating was prepared from L-phenylalanine (L-PHE) as the template, TiO 2 nanoparticles (NPs) as the support substrate, 3-aminopropyltriethoxysilane (APTES) as the functional monomer, and tetraethyl silicate (TEOS) as the cross-linker. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used for the characterization of the L-PHE@MIP(APTES-TEOS)@TiO 2 @capillary. Fourier transform infrared spectra (FT-IR), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA) were employed for the characterization of the L-PHE@MIP(APTES-TEOS)@TiO 2 . The effects of the applied voltage, pH value, buffer concentration, and acetonitrile content were investigated  experimentally to determine the optimum conditions for CEC. The best resolution for  phenylalanine enantiomers by CEC reached a value of 3.48. In addition, the specific recognition effect of L-PHE@MIP(APTES-TEOS)@TiO 2 on PHE enantiomers was studied by selective experiment. Finally, adsorption kinetic research, adsorption equilibrium isotherm study, and adsorption thermodynamic experiment were carried out to investigate the separation mechanism of PHE enantiomers with the L-PHE@MIP (APTES-TEOS)@TiO 2 @capillary, and the results were consistent with those of CEC experiments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Acid-ethanol hydrolysis and subsequent cinnamic acid (CA) esterification were employed to prepare a series of dual-modified starches efficiently loaded with curcumin (Cur) utilizing large conjugation systems provided by CA. Structures of the dual-modified starches were confirmed by IR and NMR, and their physicochemical properties were characterized by SEM, XRD and TGA. The nanoparticles fabricated from the dual-modified starch have perfect spherical shape (250.7-448.5 nm, polydispersity index <0.3), excellent biosafety (no hematotoxicity, no cytotoxicity, no mutagenicity) and high loading of Cur (up to 26.7 % loading). By XPS analysis, this high loading was believed to be supported by the synergistic effect of hydrogen bonding (provided by hydroxyl groups) and π-π interactions (provided by large conjugation system). In addition, the encapsulation of dual-modified starch nanoparticles effectively enhanced the water solubility (18-fold) and physical stability (6-8-fold) of free Cur. In vitro gastrointestinal release showed that Cur-encapsulated dual-modified starch nanoparticles were released more preferably than free Cur and that the Korsmeyer-Peppas model was the most suitable release model. These studies suggest that dual-modified starches containing large conjugation systems would be a better alternative for encapsulating fat-soluble food-derived biofunctional substances in functional food and pharmaceutical applications., 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.)

In this work, two-dimensional (2D) Zn-HMT (Zn(NO 3 ) 2 (HMT) 2 (H 2 O) 2 ] n ) nanosheets were synthesized using a facile one-step chemical precipitation in the presence of Zn(NO 3 ) 2 , hexamine (HMT), and anhydrous ethanol at room temperature. Subsequently, hexagonal T x -ZnO (T x -ZnO refers to the zinc oxide (ZnO) nanoparticles) were synthesized by a high-temperature solid-phase method at different temperatures ( x = 500, 550, 600, 650, 700, 750, and 800 °C) nanoparticles with different morphologies were synthesized by a high-temperature calcination approach using 2D Zn-HMT nanosheets as precursor. The crystal structure, morphology, specific surface areas, surface and interface properties, optical properties, and charge migration behaviors of the as-synthesized T x -ZnO nanoparticles were characterized by powder X-ray diffraction (XRD), field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), high-resolution TEM (HRTEM), automatic specific surface and aperture analyzer, X-ray photoelectron spectroscopy (XPS), UV-visible spectrophotometer, photoluminescence (PL) spectra, and electrochemical impedance spectroscopy (EIS). The photocatalytic performances and stabilities of the as-synthesized typical T x -ZnO nanoparticles with various morphologies were evaluated and compared with the commercial ZnO (CM-ZnO) nanoparticle. The T700-ZnO nanoparticle with spherical and irregular morphology exhibited the highest photocatalytic activity (99.12%) for the degradation of Rhodamine B (RhB), compared to T500-ZnO (92.32%), T600-ZnO (90.65%), T800-ZnO (44.04%), and the CM-ZnO (88.38%) nanoparticle, which can be attributed to the cooperative effects of higher crystallinity, bigger crystal size, the strongest separation efficiency, the lowest recombination rate, the fastest charge carrier transfer path, and the highest charge-transfer efficiency. The superior photocatalytic activity illustrated by the T700-ZnO nanoparticle makes it have potential application prospects for the treatment of organic wastewater.

Aptamers with high affinity and specificity for certain targets have rapidly become a novel class of targeted ligands applicated in drug delivery. Based on the excellent characteristics of aptamers, different aptamer-mediated drug delivery systems have been developed, including aptamer-drug conjugate (ApDC), aptamer-siRNA, and aptamer-functionalized nanoparticle systems for the effective treatment of cancer, which can reduce potential toxicity and improve therapeutic efficacy. In this review, we summarize the recent progress of aptamer-mediated delivery systems in cancer therapy, and discuss the application prospects and existing problems of innovative approaches based on aptamer therapy. Overall, this review aims to better understand the current aptamer-based targeted delivery applications through in-depth analysis to improve efficacy and develop new therapeutic methods which can ultimately improve treatment outcomes for cancer patients., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Helicobacter pylori (H. pylori) is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with >90% eradication rates on a consistent basis. However, the overuse of antibiotics causes H. pylori to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of H. pylori . Additionally, we discuss current challenges in this field and future perspectives that may be used in anti- H. pylori strategies., Competing Interests: The authors declare that there are no competing interests., (© 2023 Yin et al.)

Phototherapy is a new method to treat tumor, including photodynamic therapy (PDT) and photothermal therapy (PTT). However, the GSH in tumor cells could deplete ROS produced by photosensitizers, resulting in inadequate PDT. Isothiocyanate not only is a new type of anti-tumor drug, but also may combine with GSH, increasing the content of intracellular ROS and improving PDT effect. Here we synthesized a kind of water-soluble nanoparticles (BN NPs) parceling BODIPY-I-35 up with mPEG-ITC and lecithin. mPEG-ITC can react with GSH in tumor cells to reduce the consumption of ROS. BN NPs can be used as vectors to deliver drugs to tumor sites. Under 808 nm laser irradiation, BN NPs solution increased 13 °C within 10 min, indicating that BN NPs had superb photothermal performance. In vitro experiments, low dose BN NPs showed satisfactory PDT and PTT effects, and the cell viability of MCF-7 cell was only 13%. In vivo, BN NPs with excellent biocompatibility showed favorable phototherapy effect and tumor was effectively inhibited. Fluorescence imaging could present the long retention effect of BN NPs in tumor locations. In conclusion, the BN NPs showed the effect of enhancing phototherapy and provided a remarkable application prospect in the phototherapy of tumor cells., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The therapeutic effects of photothermal therapy (PTT) are dependent on the photothermal conversion efficiency of photothermal agents (PTAs) in tumors and the subsequent activation of the antitumor immune system. However, the insufficient tumor accumulation of current PTAs and the inevitable recruitment of tumor-associated macrophages (TAMs) could further compromise the antitumor activities of PTT. To address these issues, a biomimetic photothermal nanoplatform Au@Fe-PM is developed for the targeted remodeling of TAMs, which promotes the antitumor immunity of PTT. Au nanorods with second near-infrared (NIR-II) absorptions are fabricated to serve as PTAs to induce immunogenic cell death in tumor cells. The ferric hydroxide shell coated on Au nanorods can release iron ions to repolarize M2-like TAMs into the tumoricidal M1 phenotype via P38 and STAT1-mediated signaling pathways. Moreover, the surface decoration of platelet membranes endows biomimetic nanoplatform with enhanced tumor targeting ability for precise tumor ablation and TAM regulation. Consequently, Au@Fe-PM under NIR-II laser irradiation exhibits significantly higher inhibitory effects in a poor immunogenic 4T1 tumor-bearing mouse model with a 50% complete remission rate compared to conventional PTT (0%). By simultaneously reversing the immunosuppressive tumor microenvironment, this biomimetic nanoplatform offers a promising strategy for enhancing the antitumor efficacy of PTT. STATEMENT OF SIGNIFICANCE: The therapeutic effects of current photothermal therapy (PTT) are hindered by the insufficient tumor accumulation of conventional photothermal agents and the recruitment of immunosuppressive tumor-associated macrophages (TAMs) after PTT. Herein, we report a biomimetic iron-based second near-infrared (NIR-II) photothermal nanoplatform (Au@Fe-PM) for targeted TAMs reprogramming and NIR-II mediated anti-tumor immunity. Au@Fe-PM can actively target the tumor site with the help of surface-decorated platelet membranes. Meanwhile, iron ions would be released from Au@Fe-PM in acidic lysosomes to reprogram TAMs into tumoricidal M1-like macrophages, which promotes the antitumor responses elicited by NIR-II PTT, thereby contributing to remarkable tumor inhibitory effects, with 50% higher complete remission rate than that of conventional PTT., 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.)

Injectable functional biomaterials have made significant progress in cardiac regenerative. In addition, how to adjust the abominable infarction microenvironment and introduce therapeutic stem cells to improve the healing effect has become a hotspot. Herein, injectable stem cell vector is prepared by combining natural alginate hydrogel and Au@Pt nanoparticles (Au@Pt/Alg hydrogel) to encapsulate brown adipose stem cells (BASCs). Au@Pt nanoparticles with both antioxidative and conductive properties could effectively eliminate reactive oxygen species, enhance the frequency of action potential release of cardiomyocytes, and further reduce the inflammatory factors of macrophage in vitro . The Au@Pt/Alg hydrogel enhances the antioxidant, differentiation, and paracrine capability of BASCs. The effect of BASCs loaded Au@Pt/Alg hydrogel is evaluated in a rat myocardial infarction (MI) model. The antioxidant, anti-inflammatory, and heart electrical integration are showed in the MI model. More interestingly, Au@Pt/Alg hydrogel can effectively maintain the paracrine efficiency and pro-angiogenesis effects of BASCs in the infarcted area. This study led us to recognize the great value of Au@Pt/Alg hydrogels for their ability to actively regulate the microenvironment and carry stem cells for MI treatment.

Purpose: Vulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC., Methods: Polymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm 2 , 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo., Results: The prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels., Conclusion: US-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis., (© 2023. The Author(s).)

Background: Abdominal aortic aneurysms (AAAs) are a global health and economic burden. Therapeutic strategies to inhibit the progression of AAAs are currently lacking. Recently, the therapeutic effect of metformin on aneurysms has attracted considerable interest. However, the unfavorable pharmacokinetic properties of metformin limit its feasibility for AAA treatment., Methods and Results: We constructed a metformin-loaded netrin-1-responsive AAA-targeted nanoparticle (Tgt-NP-Met) for AAA management. Evaluation of the therapeutic effect of Tgt-NP-Met was performed by in vitro and in vivo experiments. Our results showed that the binding of netrin-1 monoclonal antibodies enhanced the AAA-targeting capability of nanoparticles (NPs). Moreover, Tgt-NP-Met administration prevented AAA development and reduced the aneurysm diameter in apolipoprotein E (ApoE)-deficient (ApoE -/- ) mice that received continuous infusion of angiotensin II. Furthermore, metformin prevented AAA progression by inhibiting the transformation of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a synthetic phenotype, which is mediated by macrophage infiltration and activation., Conclusion: Our findings identify metformin as a functional suppressor for macrophage-mediated phenotypic transformation of VSMCs and Tgt-NP-Met as an efficient therapeutic strategy for AAA management., Competing Interests: The authors declare that they have no competing interests in this work., (© 2023 Zhang et al.)

Immune checkpoint blockade has become a paradigm-shifting treatment modality to combat cancer, while conventional administration of immune checkpoint inhibitors, such as anti-PD-L1 antibody (α-PD-L1), often shows unsatisfactory immune responses and lead to severe immune-related adverse effects (irAEs). Herein, we develop a PD-L1 aptamer-based spherical nucleic acids (SNAs), which consists of oxaliplatin (OXA) encapsulated in a metal-organic framework nanoparticle core and a dense shell of aptPD-L1 (denoted as M@O-A). Upon light irradiation, this nanosystem enables concurrent photodynamic therapy (PDT), chemotherapy, and enhanced immunotherapy in one shot to inhibit both primary colorectal tumors and untreated distant tumors in mice. Notably, M@O-A shows scarcely any systemic immunotoxicity in a clinical irAEs-mimic transgenic mouse model. Collectively, this study presents a novel strategy for priming robust photo-immunotherapy against cancer with enhanced safety., (© 2022 Wiley-VCH GmbH.)

Ibrutinib (IBR) is an oral covalent inhibitor of Bruton's tyrosine kinase (BTK) that has been approved for the treatment of hematological malignancies. It was reported that IBR exhibited great therapeutic potential for glioma. However, the poor water solubility and high hepatic first-pass effect restrict its anti-glioma application. Meanwhile, IBR induces cytoprotective autophagy through Akt/mTOR signaling pathway, thus leading to a compromised antitumor effect. Herein, we aimed to develop a human serum albumin (HSA) based co-delivery system (IBR&HCQ HSA NPs) encapsulating IBR and hydroxychloroquine (HCQ). The bioavailability of IBR was largely improved, and enhanced sensitivity of glioma to IBR was achieved due to inhibition effect of HCQ on IBR-induced pro-survival autophagy. The physicochemical properties of IBR&HCQ HSA NPs were characterized to optimize the formulation. Biodistribution investigation revealed that HSA NPs (20 mg/kg, i.v.) dramatically increased the accumulation of IBR in glioma, which was 5.59 times higher than that of free IBR (100 mg/kg, i.g.). CCK-8 and apoptosis assays demonstrated that IBR&HCQ HSA NPs showed maximal cytotoxicity to C6 cells. In vivo studies indicated that the survival time was significantly prolonged in IBR&HCQ HSA NPs treated mice compared to those treated with IBR HSA NPs. Taken together, the HSA-based drug delivery system of IBR and HCQ opens a new avenue for efficient treatment of glioma., 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 B.V. All rights reserved.)

Introduction: Dry eye disease (DED) is a multifactor-induced disease accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Traditional anti-inflammation agent corticosteroids applied in DED treatment could result in high intraocular pressure, especially in long-term treatment. Therefore, we explored a nano drug that aimed to block the formation pathway of DED which had anti-inflammatory, sustained release, and good biocompatibility characteristics in this study., Methods: We prepared a novel nanomedicine (Tet-ATS@PLGA) by the thin film dispersion-hydration ultrasonic method and detected its nanostructure, particle size, and zeta potential. Flow cytometry was used to detect the cell survival rate of each group after 24 h of drug treatment on inflammed Statens Seruminstitut Rabbit Corneal (SIRC) cells. Observed and recorded corneal epithelial staining, tear film rupture time, and Schirmer test to detect tear secretion on the ocular surface of rabbits. The corneal epithelial thickness, morphology, and number of bulbar conjunctival goblet cells were recorded by H&E staining. Finally, we detected the expression of VEGF, IL-1β, PGE2, and TNF-α by cellular immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA)., Results: The encapsulation efficiency and drug loading of Tet-ATS@PLGA were 79.85% and 32.47%, respectively. At eye surface temperature, Tet can easily release from Tet-ATS@PLGA while that it was difficult to release at storage temperature and room temperature. After 2 weeks medication, Tet-ATS@PLGA can effectively improve the tear film rupture time and tear secretion time in a DED model (p &lt;0.05). Compared with the normal group (62.34 ± 4.86 mm), the thickness of corneal epithelium in ATS (29.47 ± 3.21 mm), Tet-ATS (46.23 ± 2.87 mm), and Tet-ATS@PLGA (55.76 ± 3.95 mm) gradually increased. Furthermore, the flow cytometry indicated that Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory SIRC cells, and the cellular immunofluorescence and ELISA experiments showed that the expression intensity of inflammatory factors such as VEGF, IL-1β, PGE2, and TNF-α decreased in this process. Interestingly, Tet also had the effect of reducing intraocular pressure., Conclusion: Tet-ATS@PLGA can effectively promote the apoptosis of inflammatory corneal epithelial cells, thus inhibiting the expression of inflammatory factors to block the formation of DED and improve the secretion of tear on the ocular surface., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Existing ferroptosis as an iron-dependent form of regulated cell death primarily relies on importing exogenous iron. However, the excessive employment of toxic materials may cause potential adverse effects on human health. Herein, a ferritin-hijacking nanoparticle (Ce6-PEG-HKN 15 ) is fabricated, by conjugating the ferritin-homing peptide HKN 15 with the photosensitizer chlorin e6 (Ce6) for endogenous ferroptosis without introducing Fenton-reactive metals. Once internalized, the designed Ce6-PEG-HKN 15 NPs can specifically accumulate around ferritin. With laser irradiation, the activated Ce6 in nanoparticles potently generates reactive oxygen species (ROS) surrounding ferritin. Abundant ROS not only helps to destroy the iron storage protein and activate endogenous ferroptosis but also directly kill tumor cells. In turn, the released iron partially interacts with intracellular excess H 2 O 2 to produce O 2 , thereby enhancing photodynamic therapy and further amplifying oxidative stress. Overall, this work highlights the possibility of endogenous ferroptosis via spatiotemporally destroying ferritin, offering a paradigm for synergistic ferroptosis-photodynamic antitumor therapy., (© 2022 Wiley-VCH GmbH.)

A series of cinnamic acid (CA)-esterified debranched starch (CDS) containing aromatic systems were prepared and successfully fabricated as nanoparticles to encapsulate curcumin by taking advantage of the additional π-π interactions provided from CA. The CDS nanoparticles (CDS NPs) have good dispersion (polydispersity index of 0.124-0.314) and sizes range of 130-330 nm. The excellent biosafety of CDS NPs was demonstrated by hemolysis, cytotoxicity and mutagenicity assays. Efficient encapsulation (LC = 26.86 %) and sustained release of curcumin were achieved, and the curcumin-encapsulated CDS NPs (CDS-Cur NPs) increased 266-fold water solubility and 2.3-6.5-fold photothermal stability for curcumin, compared to free curcumin. Functional studies showed that CDS-Cur NPs exhibited superior biofilm scavenging ability, with a 2-4.3-fold improvement compared to free curcumin. In addition, CDS-Cur NPs also exhibited far superior antibacterial effects than free curcumin in a bacteriostatic food model of chicken breast. This study not only provides a new scheme for the efficient loading of curcumin, but also provides new ideas for the usage of starch-based materials in antibacterial applications., 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.)

Exploring polymeric nanoplatforms combined with reactive oxygen species (ROS) responsiveness with mitochondria targeting has emerged as an effective strategy for enhanced photodynamic therapy (PDT). Amphiphilic copolymers were synthesized by reacting acrylamide thioketal (TK) linkers with amino-terminated triphenylphosphonium-polyethylene glycol and dodecylamine for encapsulating chlorin e6 (Ce6) via self-assembly. Then, anionic cladding with tumor targeting deshelled in tumor acidic microenvironments was surface-anchored by electrostatic forces (BioPEGDMA@RM). After sequential targeting to the mitochondria of cancerous cells, BioPEGDMA@RM could be light-activated with Ce6 released upon ROS cleavage of TK linkages. It was found that Ce6-loaded BioPEGDMA@RM exhibited higher cytotoxicity on CT26 cells and performed stronger ability on the production of ROS than that without TK linkers. Moreover, a minimum illumination of 3 and 5 min could be required for achieving the maximum release of Ce6 and high in vitro cytotoxicity for Ce6-loaded BioPEGDMA@RM, respectively. Furthermore, Ce6-loaded BioPEGDMA@RM showed 1.29-fold and 1.21-fold higher tumor inhibition on BALB/c nude mice and Kunming mice and stimulated immunologic reactions with more generation of IFN-γ and TNF-α and activation of CD3 + , CD4 + , and CD8 + T-lymphocytes and DCs than that of Ce6-loaded nanoparticles without TK bonds. This work provided an academic reference for the development of ROS-responsive drug delivery systems for advanced PDT efficiency.

Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Activated fibroblast-like synovial (FLS) cells are regarded as an important target for rheumatoid arthritis (RA) treatment via starvation therapy mediated by glucose oxidase (GOx). However, the hypoxic RA-FLS environment greatly reduces the oxidation process of glucose and leads to a poor therapeutic effect of the GOx-based starvation therapy. In this work, we designed a hollow mesoporous copper sulfide nanoparticles (CuS NPs)-based smart GOx/atovaquone (ATO) codelivery system (named as V-HAGC) targeting RA-FLS cells to realize a O 2 -economized dual energy inhibition strategy to solve the limitation of GOx-based starvation therapy. V-HAGC armed with dual multi-stimuli-responsive "doorkeepers" can guard drugs intelligently. Once under the stimulation of photothermal and acidic conditions at the targeted area, the dual intelligent responsive "doors" would orderly open to realize the controllable release of drugs. Besides, the efficacy of V-HAGC would be much improved by the additional chemodynamic therapy (CDT) and photothermal therapy (PTT) stimulated by CuS NPs. Meanwhile, the upregulated H 2 O 2 and acid levels by starvation therapy would promote the Fenton-like reaction of CuS NPs under O 2 -economized dual energy inhibition, which could enhance the PTT and CDT efficacy as well. In vitro and in vivo evaluations revealed V-HAGC with much improved efficacy of this combination therapy for RA. In general, the smart V-HAGC based on the O 2 -economized dual energy inhibition strategy combined with enhanced CDT and PTT has the potential to be an alternative methodology in the treatment of RA.

There is an urgent need to develop photosensitive nanoenzymes with better phototherapeutic efficiency through simple processes. By exploiting semiconductor catalysis and defect chemistry principles, herein, a MnMoO x composite semiconductor nanoenzyme was developed to achieve a fully integrated theranostic nanoenzyme for highly efficient photo/chemo-enzyme-dynamic eradication of deep tumors. Relative to iron oxides, manganese oxides offer ideal catalytic performance under near-neutral conditions, which helps to broaden the suitable pH range of the MnMoO x nanoenzyme for antitumor therapy. Furthermore, with the assistance of glutathione depletion, Mn 4+ /Mo 6+ was successfully converted to Mn 2+ /Mo 5+ , inhibiting the scavenging of reactive oxygen species (ROS) and promoting cycling. Therefore, MnMoO x has favorable catalase (CAT)-like activity and oxidase (OXD)-like activity in the tumor microenvironment (TME) for promoting the "H 2 O 2 O 2 O 2 - " and "H 2 O 2 OH" cascade reactions. The abundant oxygen vacancy defects also promote the surface plasmon resonance (SPR) effect in the second near-infrared (NIR-II) window of MnMoO x , which significantly enhanced its photothermal therapy (PTT) effect and catalytic activity. In detail, ROS production was significantly enhanced due to the adsorption of water and oxygen molecules by the rich oxygen vacancies of MnMoO x . MnMoO x also exhibited excellent multi-modal imaging activity (including computed tomography (CT), magnetic resonance imaging (MRI), and photoacoustic (PA)), which can be exploited to better guide the administration of medication., 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 Inc. All rights reserved.)

Extracellular vesicles (EVs) have attracted attention as delivery vehicles due to their structure, composition, and unique properties in regeneration and immunomodulation. However, difficulties during production and isolation processes of EVs limit their large-scale clinical applications. EV mimetics (EVMs), prepared via top-down strategies that improve the yield of nanoparticles while retaining biological properties similar to those of EVs have been used to address these limitations. Herein, the preparation of EVMs is reviewed and their characteristics in terms of structure, composition, targeting ability, cellular uptake mechanism, and immunogenicity, as well as their strengths, limitations, and future clinical application prospects as EV alternatives are summarized., (© 2022 Wiley-VCH GmbH.)

Focused ultrasonic ablation surgery (FUAS) for tumor treatment has emerged as an effective non-invasive therapeutic approach, but its widespread clinical utilization is limited by its low therapeutic efficiency caused by inadequate tumor targeting, single imaging modality, and possible tumor recurrence following surgery. Therefore, this study aimed to develop a biological targeting synergistic system consisting of genetically engineered bacteria and multi-functional nanoparticles to overcome these limitations. Escherichia coli was genetically modified to carry an acoustic reporter gene encoding the formation of gas vesicles (GVs) and then target the tumor hypoxic environment in mice. After E. coli producing GVs (GVs-E. coli) colonized the tumor target area, ultrasound imaging and collaborative FUAS were performed; multi-functional nanoparticles were then enriched in the tumor target area through electrostatic adsorption. Multi-functional cationic lipid nanoparticles containing IR780, perfluorohexane, and banoxantrone dihydrochloride (AQ4N) were coloaded in the tumor to realize targeted multimodal imaging and enhance the curative effect of FUAS. AQ4N was stimulated by the tumor hypoxic environment and synergistically cooperated with FUAS to kill tumor cells. In sum, synergistic tumor therapy involving multi-functional nanoparticles mediated by genetically engineered bacteria overcomes the limitations and improves the curative effect of existing FUAS. STATEMENT OF SIGNIFICANCE: Inadequate tumor targeting, single image monitoring mode, and prone tumor recurrence following surgery remain significant challenges yet critical for tumor therapy. This study proposes a strategy for genetically engineered bacteria-mediated multifunctional nanoparticles for synergistic tumor therapy. The multifunctional genetically engineered biological targeting synergistic agent can accomplish tumor-targeting therapy, synergistic FUAS ablation, hypoxia-activated chemotherapy combined with FUAS ablation, and multiple-imaging guidance and monitoring all at the same time, thereby compensating for the shortcomings of FUAS treatment. This strategy could pave the way for the progress of tumor therapy., 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 Ltd.)

The combination therapy of strengthening inflammation regression and mucosal repair may overcome the "therapeutic ceiling" of ulcerative colitis (UC). However, poor targeting is an outstanding challenge in the preparation of drug delivery systems for UC treatment. Here, we developed anti-inflammatory drug (patchouli alcohol, PA)-loaded nanoparticles (NPs) derived from natural silk fibroin (SF) and subjected to surface functionalization with cyclo RGD peptide (cRGD). Self-assembled SF NPs realized sustained drug release. Meanwhile, cRGD functionalization yielded notably targeted drug delivery to inflamed colon, and thereby enhanced the anti-inflammatory and barrier repair capabilities of NPs. Moreover, cRGD-PASFNs regulated innate immune responses and exerted a potent therapeutic efficacy against acute colitis. Surprisingly, the cRGD-PASFNs also modulated the abnormal level of amino acids which are crucial to the integrity of the intestinal barrier. Additionally, oral delivery of this nanomedicine displayed an excellent safety profile in the mouse model. This study confers confidence for the further development of targeted precision therapy for UC and other inflammatory diseases., Competing Interests: Declaration of competing interest This article has not been published elsewhere in whole or in part. There are no ethical/legal conflicts involved in the paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Glucose oxidase (GOx)-based starvation therapy is a new cancer treatment strategy. However, the characteristics such as limited curative effect and hypoxic tumor environment hinder its further application seriously., Methods: Herein, doxorubicin (DOX) loaded in hollow mesoporous copper sulfide (HMCuS) nanoparticles assembled with manganese dioxide (HMMD) as nanoshell was prepared. We developed a targeted enhanced cancer treatment method to camouflage HMMD by GOx-functionalized platelet (PLT) membranes (HMMD@PG)., Results: GOx can be specially transported to the tumor site with PLT membrane for effective starvation treatment. Glucose and oxygen (O 2 ) in the tumor were converted to H 2 O 2 under the catalysis of GOx. HMMD can catalyze H 2 O 2 to produce O 2 and consume glutathione (GSH) in time, which regulates the tumor microenvironment (TME) and improves the adverse conditions of anti-tumor. In addition, DOX encapsulated in HMCuS-MnO 2 release was accelerated from the nanoparticles after the "gatekeeper" MnO 2 is consumed. The study of anti-tumor mechanism shows that the remarkable tumor suppressive ability of HMMD@PG comes from the three peaks synergy of starvation treatment, photothermal treatment (PTT), and chemotherapy. This nanoplatform disguised by PLT membrane has significant tumor inhibition ability, good biocompatibility and almost has no side effects in main organs., Conclusion: This work broadens the application mode of GOx and shows the new development of a multi-mode collaborative processing system of nanoplatforms based on cell membrane camouflage., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Du et al.)

Chemokines control the migratory patterns and positioning of immune cells to organize immune responses to pathogens. However, many chemokines have been associated with systemic autoimmune diseases that have chronic IFN signatures. We report that a series of chemokines, including CXCL4, CXCL10, CXCL12, and CCL5, can superinduce type I IFN (IFN-I) by TLR9-activated plasmacytoid DCs (pDCs), independently of their respective known chemokine receptors. Mechanistically, we show that chemokines such as CXCL4 mediate transcriptional and epigenetic changes in pDCs, mostly targeted to the IFN-I pathways. We describe that chemokines physically interact with DNA to form nanoparticles that promote clathrin-mediated cellular uptake and delivery of DNA in the early endosomes of pDCs. Using two separate mouse models of skin inflammation, we observed the presence of CXCL4 associated with DNA in vivo. These data reveal a noncanonical role for chemokines to serve as nucleic acid delivery vectors to modulate TLR signaling, with implications for the chronic presence of IFN-I by pDCs in autoimmune diseases., (© 2022 Du et al.)

Purpose: Breast cancer is detrimental to the health of women due to the difficulty of early diagnosis and unsatisfactory therapeutic efficacy of available breast cancer therapies. High intensity focused ultrasound (HIFU) ablation is a new method for the treatment of breast tumors, but there is a problem of low ablation efficiency. Therefore, the improvement of HIFU efficiency to combat breast cancer is immediately needed. This study aimed to describe a novel anaerobic bacteria-mediated nanoplatform, comprising synergistic HIFU therapy for breast cancer under guidance of ultrasound (US) and magnetic resonance (MR) bimodal imaging., Methods: The PFH@CL/Fe 3 O 4 nanoparticles (NPs) (Perfluorohexane (PFH) and superparamagnetic iron oxides (SPIO, Fe 3 O 4 ) with cationic lipid (CL) NPs) were synthesized using the thin membrane hydration method. The novel nanoplatform Bifidobacterium bifidum- mediated PFH@CL/Fe 3 O 4 NPs were constructed by electrostatic adsorption. Thereafter, US and MR bimodal imaging ability of B. bifidum- mediated PFH@CL/Fe 3 O 4 NPs was evaluated in vitro and in vivo. Finally, the efficacy of HIFU ablation based on B. bifidum- PFH@CL/Fe 3 O 4 NPs was studied., Results: B. bifidum combined with PFH@CL/Fe 3 O 4 NPs by electrostatic adsorption and enhanced the tumor targeting ability of PFH@CL/Fe 3 O 4 NPs. US and MR bimodal imaging clearly displayed the distribution of the bio-targeting nanoplatform in vivo. It was conducive for accurate and effective guidance of HIFU synergistic treatment of tumors. Furthermore, PFH@CL/Fe 3 O 4 NPs could form microbubbles by acoustic droplet evaporation and promote efficiency of HIFU ablation under guidance of bimodal imaging., Conclusion: A bio-targeting nanoplatform with high stability and good physicochemical properties was constructed. The HIFU synergistic agent achieved early precision imaging of tumors and promoted therapeutic effect, monitored by US and MR bimodal imaging during the treatment process., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Jiang et al.)