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Multifunctional food packaging composite films were prepared using Pediococcus acidilactici J1 exopolysaccharide (EPS), potato starch (PS) and TiO 2 nanoparticles by casting method. The microstructure, physicochemical properties and antibacterial activity of EPS/PS composite films with different weight ratio of TiO 2 nanoparticles were characterized. Transmission electron microscope (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM) revealed the uniform distribution of TiO 2 nanoparticles in the EPS/PS matrix. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) results indicated that the interaction between polymers and nanoparticles through non-covalent bonds. When TiO 2 nanoparticles were added at 1 % (wt), the composite film had higher barrier properties against water vapor and UV-vis light, and better mechanical properties then EPS/PS film. Notably, EPS/PS/1%TiO 2 composite film exhibited good antioxidant and antibacterial activity against Escherichia coli and Staphylococcus aureus. Through the analysis of the quality indexes and microbial community structure during the storage of chilled meat, the composite film slowed the oxidation rate of chilled meat and inhibited the growth of dominant spoilage bacteria, effectively extending its shelf life. All results suggested that EPS/PS/1%TiO 2 composite film could serve as an effective packaging material for chilled meat, providing a novel approach to solve its limited shelf-life problem., 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.)

In recent years, significant advances in enhancing the quantum yield (QY) of trivalent lanthanide (Ln 3+ ) ion-based nanoparticles have been achieved through photosensitization, using host matrices or capping organic ligands as photosensitizers to absorb incoming photons and transfer energy to the Ln 3+ ions. The Ln 3+ ion-based nanoparticles possess several excellent fluorescent properties, such as nearly constant transition energies, atomic-like sharp transitions, long emission lifetimes, large Stokes shifts, high photostability, and resistance to photobleaching; these properties make them more promising candidates as next-generation fluorescence probes in the visible region, compared with other traditional materials such as organic dyes and quantum dots. However, their QYs are generally low and thus need to be improved to facilitate and extend their applications. Considerable efforts have been made to improve the QYs of Ln 3+ ion-based nanoparticles through photosensitization. These efforts include the doping of Ln 3+ ions into host matrices or capping the nanoparticles with organic ligands. Among the Ln 3+ ion-based nanoparticles investigated in previous studies, this review focuses on those containing Eu 3+ , Tb 3+ , and Dy 3+ ions with red, green, and yellow emission colors, respectively. The emission intensities of Eu 3+ and Tb 3+ ions are stronger than those of other Ln 3+ ions; therefore, the majority of the reported studies focused on Eu 3+ and Tb 3+ ion-based nanoparticles. This review discusses the principles of photosensitization, several examples of photosensitized Ln 3+ ion-based nanoparticles, and in vitro and in vivo biomedical fluorescent imaging (FI) applications. This information provides valuable insight into the development of Ln 3+ ion-based nanoparticles with high QYs through photosensitization, with future potential applications in biomedical FI.

While polyphenolic substances stand as excellent antibacterial agents, their antimicrobial properties rely on the auxiliary support of micro-/nanostructures. Despite offering a novel avenue for enhancing polymer performance, controllable fabrication of mesoporous polymeric nanomaterials encounters significant challenges due to intricate intermolecular forces. In this article, mesoporous catechin nanoparticles have been successfully fabricated using a balanced multivariate interaction approach. The harmonization of the water-ethanol ratio and ionic strength effectively balances the forces of hydrogen bonding and π-π stacking, facilitating the controlled assembly of mesostructures. The mesoporous catechin nanoparticles exhibit a uniform spherical structure (∼100 nm), open mesopores with a diameter of ∼15 nm, and a high surface area of ∼106 m 2 g -1 . While exhibiting a good biocompatibility and negative surface charge, the mesoporous catechins possess outstanding antibacterial ability and function as an antibiotic mesoformulation without the necessity of loading any drugs. This mesoformulation inhibits 50% in vitro Staphylococcus aureus growth with a low concentration of ∼10 μg mL -1 and achieves complete inhibition at ∼25 μg mL -1 . In a mouse wound model, accelerated wound healing and complete closure within 6-8 days are achieved. Proteomics of bacteria reveals that the excellent antibacterial property is attributed to the synergetic effect of mesoformulation's mesostructure and the catechin molecule intervening in bacterial metabolism. Overall, this work may pave a novel way for the future exploration of polymer nanomaterials and antibiotic formulations.

Controlling and reducing plaque formation plays a pivotal role in preventing and treating periodontal disease, often utilizing antibacterial drugs to enhance therapeutic outcomes. Mesoporous silica nanoparticles (MSN), an FDA-approved inorganic nanomaterial, possess robust physical and chemical properties, such as adjustable pore size and pore capacity, easy surface modification, and high biosafety. Numerous studies have exploited MSN to regulate drug release and facilitate targeted delivery. This study aimed to synthesize an MSN-tetracycline (MSN-TC) complex and investigate its inhibitory potential on Porphyromonas gingivalis (P. gingivalis)-induced bone resorption. The antibacterial efficacy of MSN-TC was evaluated through bacterial culture experiments. A P. gingivalis-induced bone resorption model was constructed by subcutaneously injecting P. gingivalis around the cranial bone of rats. Micro-computed tomography was employed to assess the inhibitory impact of MSN and MSN-TC on bone resorption. Furthermore, the influence of MSN and MSN-TC on osteoclast differentiation was examined in vitro. The MSN exhibited optimal pore size and particle dimensions for effective loading and gradual release of TC. MSN-TC demonstrated significant bacteriostatic activity against P. gingivalis. MSN-TC-treated rats showed significantly reduced cranial bone tissue destruction compared to MSN or TC-treated rats. Additionally, both MSN and MSN-TC exhibited inhibitory effects on the receptor activator of nuclear factor kappa-Β ligand-mediated osteoclast differentiation. The MSN-TC complex synthesized in this study demonstrated dual efficacy by exerting antibacterial effects on P. gingivalis and by resisting osteoclast differentiation, thereby mitigating bone resorption induced by P. gingivalis., (© 2024. The Author(s).)

The sensitive detection of foodborne pathogenic and rapid antibiotic susceptibility testing (AST) is of great significance. This paper reports the enzyme-triggered in situ synthesis of yellow emitting silicon nanoparticles (SiNPs) and the detection of Escherichia coli (E. coli) O157:H7 in food samples and the rapid AST. The rapid counting of E. coli O157:H7 has been achieved through direct visual observation, equipment detection, and smartphone digitalization. A simple detection platform based on smartphone senses and cotton swabs has been established. Meanwhile, rapid AST based on enzyme-catalyzed SiNPs can intuitively obtain colorimetric samples. This paper established a system for bacterial enzyme-triggered in situ synthesis of SiNPs, with high responsiveness, luminescence ratio, and specificity. The detection limit for E. coli O157:H7 can reach 100 CFU/mL during 5 h, and the recovery efficiency ranges from 90.14% to 110.16%, which makes it a promising strategy for the rapid detection of E. coli O157:H7 and AST., 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 Ltd. All rights reserved.)

Bio-stimulants, such as selenium nanoparticles and melatonin, regulate melon growth. However, the effects of individual and combined applications of selenium nanoparticles and melatonin on the growth of melon seedlings have not been reported. Here, two melon cultivars were sprayed with selenium nanoparticles, melatonin, and a combined treatment, and physiological and biochemical properties were analyzed. The independent applications of selenium nanoparticles, melatonin, and their combination had no significant effects on the plant heights and stem diameters of Jiashi and Huangmengcui melons. Compared with the controls, both selenium nanoparticle and melatonin treatments increased soluble sugars (6-63%) and sucrose (11-88%) levels, as well as the activity of sucrose phosphate synthase (171-237%) in melon leaves. The phenylalanine ammonia lyase (29-95%), trans cinnamate 4-hydroxylase (32-100%), and 4-coumaric acid CoA ligase (26-113%), as well as mRNA levels, also increased in the phenylpropanoid metabolism pathway. Combining the selenium nanoparticles and melatonin was more effective than either of the single treatments. In addition, the levels of superoxide dismutase (43-130%), catalase (14-43%), ascorbate peroxidase (44-79%), peroxidase (25-149%), and mRNA in melon leaves treated with combined selenium nanoparticles and melatonin were higher than in controls. The results contribute to our understanding of selenium nanoparticles and melatonin as bio-stimulants that improve the melon seedlings' growth by regulating carbohydrate, polyamine, and antioxidant capacities.

Rationale: NLRP3 inflammasome is critical in the development and progression of many metabolic diseases driven by chronic inflammation, but its effect on the pathology of postmenopausal osteoporosis (PMOP) remains poorly understood. Methods: We here firstly examined the levels of NLRP3 inflammasome in PMOP patients by ELISA. Then we investigated the possible mechanisms underlying the effect of NLRP3 inflammasome on PMOP by RNA sequencing of osteoblasts treated with NLRP3 siRNA and qPCR. Lastly, we accessed the effect of decreased NLRP3 levels on ovariectomized (OVX) rats. To specifically deliver NLRP3 siRNA to osteoblasts, we constructed NLRP3 siRNA wrapping osteoblast-specific aptamer (CH6)-functionalized lipid nanoparticles (termed as CH6-LNPs-siNLRP3). Results: We found that the levels of NLRP3 inflammasome were significantly increased in patients with PMOP, and were negatively correlated with estradiol levels. NLRP3 knock-down influenced signal pathways including immune system process, interferon signal pathway. Notably, of the top ten up-regulated genes in NLRP3-reduced osteoblasts, nine genes (except Mx2) were enriched in immune system process, and five genes were related to interferon signal pathway. The in vitro results showed that CH6-LNPs-siNLRP3 was relatively uniform with a dimeter of 96.64 ± 16.83 nm and zeta potential of 38.37 ± 1.86 mV. CH6-LNPs-siNLRP3 did not show obvious cytotoxicity and selectively delivered siRNA to bone tissue. Moreover, CH6-LNPs-siNLRP3 stimulated osteoblast differentiation by activating ALP and enhancing osteoblast matrix mineralization. When administrated to OVX rats, CH6-LNPs-siNLRP3 promoted bone formation and bone mass, improved bone microarchitecture and mechanical properties by decreasing the levels of NLRP3, IL-1β and IL-18 and increasing the levels of OCN and Runx2. Conclusion: NLRP3 inflammasome may be a new biomarker for PMOP diagnosis and plays a key role in the pathology of PMOP. CH6-LNPs-siNLRP3 has potential application for the treatment of PMOP., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Epirubicin (EPI) alone can trigger mildly protective autophagy in residual tumor cells, resulting in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and leads to antiprogrammed death ligand 1 (anti-PD-1)/PD-L1 therapy resistance, posing a significant clinical challenge in tumor immunotherapy. The combination of checkpoint inhibitors targeting the PD-1/PD-L1 pathway and amplifying autophagy presents an innovative approach to tumor treatment, which can prevent tumor immune escape and enhance therapeutic recognition. Herein, we aimed to synthesize a redox-triggered autophagy-induced nanoplatform with SA&EA-induced PD-L1 inhibition. The hyaluronic acid (HA) skeleton and arginine segment promoted active nanoplatform targeting, cell uptake, and penetration. The PLGLAG peptide was cleaved by overexpressing matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, and the PD-L1 inhibitor D-PPA was released to inhibit tumor immune escape. The intense autophagy inducers, STF-62247 and EPI, were released owing to the cleavage of disulfide bonds influenced by the high glutathione (GSH) concentration in tumor cells. The combination of EPI and STF induced apoptosis and autophagic cell death, effectively eliminating a majority of tumor cells. This indicated that the SA&EA nanoplatform has better therapeutic efficacy than the single STF@AHMPP and EPI@AHMPTP groups. This research provided a way to set up a redox-triggered autophagy-induced nanoplatform with PD-L1 inhibition to enhance chemo-immunotherapy.

Exosome-like nanoparticles (ELNs) are novel naturally occurring plant ultrastructures and contain unique bioactive components. However, the potential applications and biological functions of plant ELNs, especially in the context of health promotion and disease prevention, remain largely unexplored. This study aimed to explore the biological activities and functional mechanisms of Actinidia arguta -derived exosome-like nanoparticles (AAELNs). We reported the development of AAELNs, which possess particle sizes of 157.8 nm and a negative surface charge of -23.07 mV, uptaking by RAW264.7 cells, and reduction of oxidative stress by decreasing the activity of GSH-Px and T-SOD and increasing the content of MDA. Through the use of high-throughput sequencing technology, 12 known miRNA families and 23 additional miRNAs were identified in AAELNs, GO and KEGG term enrichment analysis revealed the potential of AAELNs-miRNAs in modulating neural-relevant behaviors. Additionally, LC-MS/MS analysis detected a total of 32 major lipid classes, 430 lipid subclasses, and 1345 proteins in AAELNs. Furthermore, in vivo fluorescence disappearance and in vitro fermentation experiments demonstrated that AAELNs were able to enter the colon and improve the microbial structure. These findings suggest that AAELNs could serve as nanoshuttles in food, potentially offering health-enhancing properties.

Background: Previous studies have confirmed the antioxidant and anti-inflammatory effects of active ginseng components that protect against liver injury. However, ginseng-derived nanoparticles (GDNPs), low-immunogenicity nanovesicles derived from ginseng, have not been reported to be hepatoprotective., Purpose: In this study, we investigated whether GDNPs could attenuate alcohol-induced liver injury in LO 2 cells and mice by modulating oxidative stress and inflammatory pathways, thereby advancing the theoretical basis for the development of novel pharmacological treatments., Study Design: Alcohol was used to construct in vitro and in vivo models of alcoholic liver injury. To explore the mechanisms by which GDNPs exert their protective effects against alcoholic liver injury, we examined the expression of oxidative stress-related genes and analysed inflammatory responses in vitro and in vivo. The experimental findings were verified using network pharmacology., Methods: The composition of the GDNPs was analysed using liquid chromatography-mass spectrometry. GDNPs were extracted and purified using differential ultracentrifugation and sucrose density gradient centrifugation. In vitro models of alcoholic liver injury were established using LO 2 cells, whereas C57BL/6 J mice were used as in vivo models. Oxidative stress, inflammation, and liver injury indicators were measured using appropriate kits. Levels of proteins associated with oxidative stress and inflammation were measured via western blot, while nuclear factor erythroid2-related factor 2 (Nrf2) and NF-κB protein expression was tested using immunofluorescence, immunohistochemistry, and flow cytometry. The levels of relevant transcription factors were determined using qPCR. Experimental haematoxylin and eosin staining was used to characterise the liver histological appearance and damage in mice. Network pharmacological analysis of GDNP mRNA sequencing of GDNPs was used to predict drug targets and disease associations using TCMSP., Results: GDNPs primarily included 77 compounds, including organic acids and their derivatives, amino acids and their derivatives, sugars, terpenoids, and flavonoids. GDNPs have features that allow them to be taken up by LO 2 cells and promote their proliferation. In vitro data indicated that GDNPs reduced the levels of alcohol-induced reactive oxygen species by activating the Nrf2/HO-1 signalling pathway, whilst inhibiting the NF-κB pathway and thereby reducing NO, tumour necrosis factor-α, and interleukin-1β levels to alleviate inflammation. An in vivo model showed that GDNPs improved the liver parameters and pathology in mice with alcoholic liver injury. GDNPs activate the Nrf2/HO-1/Keap1 signalling pathway in a p62-dependent manner to exert antioxidant effects. Furthermore, the TLR4/NF-κB signalling pathway was involved in the in vivo anti-inflammatory effect. Network pharmacology also confirmed that the effects of GDNPs on liver disease were associated with oxidative stress and inflammation-related targets and pathways., Conclusion: This study showed for the first time that GDNPs can alleviate alcohol-induced liver damage by activating the Nrf2/HO1 signalling pathway and blocking the NF-κB signalling pathway, thus lowering oxidative stress and inflammatory responses. Hereby, we present the Nrf2/HO1 and NF-κB signalling pathways as potential targets and GDNPs as a novel therapeutic approach for the management of alcohol-induced liver damage., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

d-Amino acids are signals for biofilm disassembly. However, unexpected metabolic pathways severely attenuate the utilization of d-amino acids in biofilm disassembly, resulting in unsatisfactory efficiency. Herein, three-dimensional poly(d-amino acid) nanoparticles (NPs), which possess the ability to block intracellular metabolism, are constructed with the aim of disassembling the biofilms. The obtained poly(α- N -acryloyl-d-phenylalanine)- block -poly(β- N -acryloyl-d-aminoalanine NPs (denoted as FA NPs) present α-amino groups and α-carboxyl groups of d-aminoalanine on their surface, which guarantees that FA NPs can effectively insert into bacterial peptidoglycan (PG) via the mediation of PG binding protein 4 (PBP4). Subsequently, the FA NPs trigger the detachment of amyloid-like fibers that connect to the PG and reduce the number of polysaccharides and proteins in extracellular polymeric substances (EPS). Finally, FA NPs damage the structural stability of EPS and lead to the disassembly of the biofilm. Based on this feature, FA NPs significantly enhance the killing efficacy of encapsulated sitafloxacin sesquihydrate (Sita) by facilitating the penetration of Sita within the biofilm, achieving complete elimination of Staphylococcal biofilm in mice. Therefore, this study strongly demonstrates that FA NPs can effectively improve biofilm disassembly efficacy and provide great potential for bacterial biofilm infection treatment.

Metabolic heterogeneity and the tumor immunosuppressive microenvironment (TIME) of triple-negative breast cancer (TNBC) hinder therapeutic effectiveness. Although emerging metabolic therapy and immunotherapy show promise, they are limited by off-target effects and immune escape. Here, a redox-activatable, sequentially-releasing nanoparticle (AMANC@M) for tumor-targeted delivery of anticancer agents and CRISPR/Cas9 has been developed. AMANC@M can reverse the TIME through dual metabolic inhibition, thereby enhancing TNBC therapy. AMANC@M demonstrates excellent biosafety and targets tumors precisely through biomimetic hybrid membrane-mediated homologous homing and the enhanced permeability and retention (EPR) effect. Once internalized into tumor cells, the CRISPR/Cas9 system ("energy nanolock") is released through glutathione (GSH) cleavage and effectively knocks down the expression of lactate dehydrogenase A (LDHA) to suppress glycolysis. After peeling off of the gene editing shell, a newly synthesized targeted drug, CPI-Z2 ("nutrihijacker" and "energy nanolock"), is released in a controlled manner to block the mitochondrial tricarboxylic acid (TCA) cycle. Nitric oxide (NO) produced from loaded L-arginine enhances the efficiency of CPI-Z2 and reduces drug resistance. Combined with NO therapy, both blockades of nutrients and energy production transform the hypoxia and acidic TIME into an immunocompetent tumor microenvironment (TME) for tumor elimination. Furthermore, AMANC@M offers capabilities for photothermal (PT) therapy and provides clear imaging through PT, photoacoustic (PA), or computed tomography (CT) signals in tumor tissue. Thus, this study provides a new and promising sequentially stimuli-responsive targeting strategy for nanoparticle development, making it a potential treatment candidate for TNBC and other tumors., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy., (© 2024. The Author(s).)

Despite its effectiveness in eliminating cancer cells, ferroptosis is hindered by the high natural antioxidant glutathione (GSH) levels in the tumor microenvironment. Herein, we developed a spatially asymmetric nanoparticle, Fe 3 O 4 @DMS&PDA@MnO 2 -SRF, for enhanced ferroptosis. It consists of two subunits: Fe 3 O 4 nanoparticles coated with dendritic mesoporous silica (DMS) and PDA@MnO 2 (PDA: polydopamine) loaded with sorafenib (SRF). The spatial isolation of the Fe 3 O 4 @DMS and PDA@MnO 2 -SRF subunits enhances the synergistic effect between the GSH-scavengers and ferroptosis-related components. First, the increased exposure of the Fe 3 O 4 subunit enhances the Fenton reaction, leading to increased production of reactive oxygen species. Furthermore, the PDA@MnO 2 -SRF subunit effectively depletes GSH, thereby inducing ferroptosis by the inactivation of glutathione-dependent peroxidases 4. Moreover, the SRF blocks Xc - transport in tumor cells, augmenting GSH depletion capabilities. The dual GSH depletion of the Fe 3 O 4 @DMS&PDA@MnO 2 -SRF significantly weakens the antioxidative system, boosting the chemodynamic performance and leading to increased ferroptosis of tumor cells.

Importance: As the most important non-magnetotactic magnetosome-producing bacteria, Acidithiobacillus ferrooxidans only requires very mild conditions to produce Fe 3 O 4 nanoparticles, thus conferring greater flexibility and potential application in biomagnetic nanoparticle production. However, the available information cannot explain the mechanism of Fe 3 O 4 nanoparticle formation in A. ferrooxidans . In this study, we applied phenomic and transcriptomic analyses to reveal this mechanism. We found that different treatment condition factors notably affect the phenomic data of Fe 3 O 4 nanoparticle in A. ferrooxidans . Using transcriptomic analyses, the gene network controlling/regulating Fe 3 O 4 nanoparticle biogenesis in A. ferrooxidans was proposed, excavating the candidate hub genes for Fe 3 O 4 nanoparticle formation in A. ferrooxidans . Based on this information, a sequential model for Fe 3 O 4 nanoparticle synthesis in A. ferrooxidans was hypothesized. It lays the groundwork for further clarifying the feature of Fe 3 O 4 nanoparticle synthesis., Competing Interests: The authors declare no conflict of interest.

While the nanobio interaction is crucial in determining nanoparticles' in vivo fate, a previous work on investigating nanoparticles' interaction with biological barriers is mainly carried out in a static state. Nanoparticles' fluid dynamics that share non-negligible impacts on their frequency of encountering biological hosts, however, is seldom given attention. Herein, inspired by badmintons' unique aerodynamics, badminton architecture Fe 3 O 4 &mPDA (Fe 3 O 4 = magnetite nanoparticle and mPDA = mesoporous polydopamine) Janus nanoparticles have successfully been synthesized based on a steric-induced anisotropic assembly strategy. Due to the "head" Fe 3 O 4 having much larger density than the mPDA "cone", it shows an asymmetric mass distribution, analogous to real badminton. Computational simulations show that nanobadmintons have a stable fluid posture of mPDA cone facing forward, which is opposite to that for the real badminton. The force analysis demonstrates that the badminton-like morphology and mass distribution endow the nanoparticles with a balanced motion around this posture, making its movement in fluid stable. Compared to conventional spherical Fe 3 O 4 @mPDA nanoparticles, the Janus nanoparticles with an asymmetric mass distribution have straighter blood flow trails and ∼50% reduced blood vessel wall encountering frequency, thus providing doubled blood half-life and ∼15% lower organ uptakes. This work provides novel methodology for the fabrication of unique nanomaterials, and the correlations between nanoparticle architectures, biofluid dynamics, organ uptake, and blood circulation time are successfully established, providing essential guidance for designing future nanocarriers.

Optical imaging in the second near-infrared window (NIR-II, 1,000-1,700 nm) holds great promise for non-invasive in vivo detection. However, real-time dynamic multiplexed imaging remains challenging due to the lack of available fluorescence probes and multiplexing techniques in the ideal NIR-IIb (1,500-1,700 nm) 'deep-tissue-transparent' sub-window. Here we report on thulium-based cubic-phase downshifting nanoparticles (α-TmNPs) with 1,632 nm fluorescence amplification. This strategy was also validated for the fluorescence enhancement of nanoparticles doped with NIR-II Er 3+ (α-ErNPs) or Ho 3+ (α-HoNPs). In parallel, we developed a simultaneous dual-channel imaging system with high spatiotemporal synchronization and accuracy. The NIR-IIb α-TmNPs and α-ErNPs facilitated the non-invasive real-time dynamic multiplexed imaging of cerebrovascular vasomotion activity and the single-cell-level neutrophil behaviour in mouse subcutaneous tissue and ischaemic stroke model., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Iron oxide nanoparticles (IONPs) have been developed as contrast agents for T 1 - or T 2 -weighted magnetic resonance imaging (MRI) on account of their excellent physicochemical and biological properties. However, general strategies to improve longitudinal relaxivity ( r 1 ) often decrease transverse relaxivity ( r 2 core-shell nanoparticles (NPs), which possess high T 1 and T 2 enhancement effect of IONPs remains a challenge. Here, we report interface regulation and size tailoring of a group of FePt@Fe 3 O 4 core-shell nanoparticles (NPs), which possess high r 1 and r 2 relaxivities. The increase of r 1 and r 2 is due to the enhancement of the saturation magnetization ( M s ), which is a result of the strengthened exchange coupling across the core-shell interface. In vivo subcutaneous tumor study and brain glioma imaging revealed that FePt@Fe 3 O 4 NPs can serve as a favorable T 1 - T 2 dual-modal contrast agent. We envision that the core-shell NPs, through interface engineering, have great potential in preclinical and clinical MRI applications.

We report an effective strategy to prepare highly ordered L 1 0 -FePt nanoparticles (NPs) by magnetic-field-assisted wet-chemical synthesis. The Mn element with high magnetic susceptibility was chosen for third-element addition, which is beneficial to reduce the required magnetic field strength for ordering transition. The evolution of morphology, ordering degree, and magnetic properties of the FePtMn nanomaterials in the synthesis process were systematically investigated. The attachment of spherical FePtMn NPs was facilitated by applying magnetic fields. The particle size was refined only when the magnetic field strength was as high as 6 T. The ordering degree and coercivity of NPs have been improved and reached the peak values when the magnetic field was 2 T, which can be easily achieved by using an ordinary electromagnet. Therefore, this work provides a feasible route for regulating the morphology and structural ordering of L 1 0 -phase ternary alloy NPs.

The ability of Janus nanoparticles to establish biological logic systems has been widely exploited, yet conventional non/uni-porous Janus nanoparticles are unable to fully mimic biological communications. Here we demonstrate an emulsion-oriented assembly approach for the fabrication of highly uniform Janus double-spherical MSN&mPDA (MSN, mesoporous silica nanoparticle; mPDA, mesoporous polydopamine) nanoparticles. The delicate Janus nanoparticle possesses a spherical MSN with a diameter of ~150 nm and an mPDA hemisphere with a diameter of ~120 nm. In addition, the mesopore size in the MSN compartment is tunable from ~3 to ~25 nm, while those in the mPDA compartments range from ~5 to ~50 nm. Due to the different chemical properties and mesopore sizes in the two compartments, we achieve selective loading of guests in different compartments, and successfully establish single-particle-level biological logic gates. The dual-mesoporous structure enables consecutive valve-opening and matter-releasing reactions within one single nanoparticle, facilitating the design of single-particle-level logic systems., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Biomineralization is a normal physiological process that includes nucleation, crystal growth, phase transformation, and orientation evolution. Notably, artificially induced biomineralization in the tumor tissue has emerged as an unconventional yet promising modality for malignancy therapy. However, the modest ion-chelating capabilities of carboxyl-containing biomineralization initiators lead to a deficient blockade, thus compromising antitumor efficacy. Herein, a biomineralization-inducing nanoparticle (BINP) is developed for blockade therapy of osteosarcoma. BINP is composed of dodecylamine-poly((γ-dodecyl-l-glutamate)-co-(l-histidine))-block-poly(l-glutamate-graft-alendronate) and combines a cytomembrane-insertion moiety, a tumor-microenvironment (TME)-responsive component, and an ion-chelating motif. After intravenous injection into osteosarcoma-bearing mice, BINP responds to the acidic TME to expose the dodecyl group on the surface of the expanded nanoparticles, facilitating their cytomembrane insertion. Subsequently, the protruding bisphosphonic acid group triggers continuous ion deposition to construct a mineralized barrier around the tumor, which blocks substance exchange between the tumor and surrounding normal tissues. The BINP-mediated blockade therapy displays tumor inhibition rates of 59.3% and 52.1% for subcutaneous and orthotopic osteosarcomas, respectively, compared with the Control group. In addition, the suppression of osteoclasts by the alendronate moiety alleviates bone dissolution and further inhibits pulmonary metastases. Hence, the BINP-initiated selective biomineralization provides a promising alternative for clinical osteosarcoma therapy., (© 2023 Wiley-VCH GmbH.)

Multi-drug combinations are a common strategy for the treatment of intracellular bacterial infections. However, different internalized pathways and the accumulation of the composite drugs at different subcellular organelles very much reduce their efficacy. Herein, an intracellular synergistic strategy is proposed, which is realized by on-site delivery of a drug combination using a macrophage/intracellular bacterium-dual targeted drug delivery system (DDS). The DDS is fabricated by encapsulating vancomycin (Van) and curcumin (Cur) into poly(α- N -acryloyl-phenylalanine)- block -poly(β- N -acryloyl-D-aminoalanine- co -2- O -acetyl-α-D-mannosyloxy) nanoparticles, denoted by (Van + Cur)@F(AM) NPs. Mannose ligands on (Van + Cur)@F(AM) NPs trigger their specific internalization in macrophages, while aminoalanine moieties subsequently drive the NPs to target intracellular methicillin-resistant Staphylococcus aureus (MRSA). Thereafter, Van and Cur are durably released in a synergistic dose at the residence site of intracellular MRSA. Under this intracellular synergistic effect, (Van + Cur)@F(AM) NPs show superior elimination efficiency in vitro and in vivo compared to the control groups, including free Van, (Van + Cur), the DDS encapsulated Van and the DDSs separately-encapsulated Van and Cur. Furthermore, (Van + Cur)@F(AM) NPs significantly enhance the in vivo antibacterial capacity by modulating the immune response. Therefore, this dual-targeted DDS-assisted intracellular synergistic antibacterial strategy of drug combination is an effective therapeutic against intracellular bacteria.

Due to non-specific strong nano-bio interactions, it is difficult for nanocarriers with permanent rough surface to cross multiple biological barriers to realize efficient drug delivery. Herein, a camouflaged virus-like-nanocarrier with a transformable rough surface is reported, which is composed by an interior virus-like mesoporous SiO 2 nanoparticle with a rough surface (vSiO 2 ) and an exterior acid-responsive polymer. Under normal physiological pH condition, the spikes on vSiO 2 are hidden by the polymer shell, and the non-specific strong nano-bio interactions are effectively inhibited. While in the acidic tumor microenvironment, the nanocarrier sheds the polymer camouflage to re-expose its rough surface. So, the retention ability and endocytosis efficiency of the nanocarrier are great improved. Owing to it's the dynamically variable rough surface, the rationally designed nanocarrier exhibits extended blood-circulation-time and enhanced tumor accumulation., (© 2023 Wiley-VCH GmbH.)

Docetaxel is a highly potent anti-tumor agent which is clinically effective for the treatment of various cancers. However, the clinical application of docetaxel is limited due to its poor solubility. The solvent and cosolvent existing in the complex solvent systems can lead to serious adverse effects in clinical application. This paper aimed to develop a novel formulation of docetaxel with improved aqueous solubility and enhanced anti-tumor efficacy. Novel albumin-bound docetaxel nanoparticles were successfully developed based on the nanoparticle albumin-bound (nab TM ) technology platform, showing a perfect particle size of 115.6 nm and high encapsulation efficiency (95.43%). Then the in vivo anti-tumor efficacy, plasma pharmacokinetics, tissue distribution and toxicity profiles of albumin-bound docetaxel nanoparticles were evaluated in comparison with those of Docetaxel Injection. The preclinical study demonstrated that albumin-bound docetaxel nanoparticles exhibited equivalent pharmacokinetic profiles, similar safety profiles and better anti-tumor efficacy on NCI-N87 human gastric carcinoma and BxPC-3 human pancreatic carcinoma compared with those of Docetaxel Injection. These results indicated that such albumin-bound docetaxel nanoparticles are promising in reducing toxicity and enhancing efficacy in clinical applications, showing great potential for developing an advanced drug delivery system for cancer 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 © 2023 Elsevier B.V. All rights reserved.)

Nanomedicine holds great promise to enhance cancer therapy. However, low active pharmaceutical ingredient (API) loading content, unpredictable drug release, and potential toxicity from excipients limit their translational capability. We herein report a full-API nanodrug composed of FDA-approved 5-aminolevulinic acid (ALA), human essential element Fe 3+ , and natural bioactive compound curcumin with an ideal API content and pH-responsive release profile for continuous spatiotemporal cancer therapy achieved by multi-step tandem endogenous biosynthesis. First, ALA enzymatically converts into photosensitizer protoporphyrin IX (PpIX). Afterward, multiple downstream products including carbon monoxide (CO), Fe 2+ , biliverdin (BV), and bilirubin (BR) are individually biosynthesized through the PpIX-heme-CO/Fe 2+ /BV-BR metabolic pathway, further cooperating with released Fe 3+ and curcumin, ultimately eliciting mitochondria damage, membrane disruption, and intracytoplasmic injury. This work not only provides a paradigm for exploiting diversified metabolites for tumor suppression, but also presents a safe and efficient full-API nanodrug, facilitating the practical translation of nanodrugs., (© 2023. The Author(s).)

Multi-component nanoparticles (mNPs) hold great potential for disease prevention and treatment. However, a major barrier is the lack of versatile platforms to accommodate steps of assembly processes of mNPs. Here the microfluidics-enabled serial assembly (MESA) of mNPs is presented. The microfluidic chip, as a mini-conveyor of initial materials, sequentially enables the assembly of sorafenib supramolecule, electrostatic adsorption of siRNA, and surface assembly of protective lipids. The produced lipid-siRNA-sorafenib nanoparticles (LSS NPs) have ultrahigh encapsulation efficiencies for sorafenib (≈100%) and siRNA (≈95%), which benefit from the accommodation of both fast and slow processes on the chip. Although carrying negative charges, LSS NPs enable cytosolic delivery of agents and high gene silencing efficiency within tumor cells. In vivo, the LSS NPs delivering hypoxia-induced factor (HIF1α)-targeted siRNA efficiently regress tumors of Hep3B xenograft and hepatocellular carcinoma patient-derived primary cells xenograft (PDCX) and finally extend the average survival of PDCX mice to 68 days. Thus, this strategy is promising as a sorafenib/siRNA combination therapy, and MESA can be a universal platform for fabricating complex nanosystems., (© 2023 Wiley-VCH GmbH.)

Introduction: As a deadly disease induced by Mycobacterium tuberculosis (Mtb), tuberculosis remains one of the top killers among infectious diseases. The low intracellular Mtb killing efficiency of current antibiotics introduced the long duration anti-TB therapy in clinic with strong side effects and increased drug-resistant mutants. Therefore, the exploration of novel anti-TB agents with potent anti-TB efficiency becomes one of the most urgent issues for TB therapies., Methods: Here, we firstly introduced a novel method for the preparation of zinc oxide-selenium nanoparticles (ZnO-Se NPs) by the hybridization of zinc oxide and selenium to combine the anti-TB activities of zinc oxide nanoparticles and selenium nanoparticles. We characterized the ZnO-Se NPs by dynamic laser light scattering and transmission electron microscopy, and then tested the inhibition effects of ZnO-Se NPs on extracellular Mtb by colony-forming units (CFU) counting, bacterial ATP analysis, bacterial membrane potential analysis and scanning electron microscopy imaging. We also analyzed the effects of ZnO-Se NPs on the ROS production, mitochondrial membrane potential, apoptosis, autophagy, polarization and PI3K/Akt/mTOR signaling pathway of Mtb infected THP-1 macrophages. At last, we also tested the effects of ZnO-Se NPs on intracellular Mtb in THP-1 cells by colony-forming units (CFU) counting., Results: The obtained spherical core-shell ZnO-Se NPs with average diameters of 90 nm showed strong killing effects against extracellular Mtb, including BCG and the virulent H37Rv, by disrupting the ATP production, increasing the intracellular ROS level and destroying the membrane structures. More importantly, ZnO-Se NPs could also inhibit intracellular Mtb growth by promoting M1 polarization to increase the production of antiseptic nitric oxide and also promote apoptosis and autophagy of Mtb infected macrophages by increasing the intracellular ROS, disrupting mitochondria membrane potential and inhibiting PI3K/Akt/mTOR signaling pathway., Discussion: These ZnO-Se NPs with synergetic anti-TB efficiency by combining the Mtb killing effects and host cell immunological inhibition effects were expected to serve as novel anti-TB agents for the development of more effective anti-TB strategy., 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 © 2023 Lin, Fan, Liao, Huang, Cong, Zhang, Jin, Zhao, Ruan, Lu, Yang, Wu, Zhao, Fu, Zheng, Xu and Pi.)

Electrochemical nitrate (NO 3 - ) reduction is a potential approach to produce high-value ammonia (NH 3 ) while removing NO 3 - nanoparticles decorated TiO 3 O 4 nanoparticles decorated TiO 2 nanoribbon array on titanium plate (Fe 3 O 4 @TiO 2 /TP) as an efficient electrocatalyst for NO 3 - -to-NH 3 conversion. When operated in 0.1 M phosphate-buffered saline and 0.1 M NO 3 - , such Fe 3 O 4 @TiO 2 /TP achieves a prominent NH 3 yield of 12394.3 μg h -1 cm -2 and a high Faradaic efficiency of 88.4%. In addition, it exhibits excellent stability during long-time electrolysis.

Iron nanoparticles (NPs) priming is known to affect the seed germination and seedling growth in many plants. However, whether it has an important role in stimulating the growth of perennial Qinghai-Tibet Plateau plants remains unclear. In this study, the effects of seed priming with different concentrations of nFe 2 O 3 and FeCl 3 (10, 50, 100, 500, and 1000 mg L -1 ) on seed germination, plant growth, photosystem, antioxidant enzyme activities, root morphology, and biomass distribution of Kobresia capillifolia were evaluated under laboratory conditions. The results showed that compared with treatment materials, concentration had more significant effects on K. capillifolia development. There was no significant impact on germination rate were discovered under all treatments, but decreased the seed mildew rate at 100 mg L -1 nFe 2 O 3 . Compare with control, Fe-based priming significantly decreased root biomass. All Fe-based treatments increased rubisco activity of leaves, and significantly enhanced Pn at ranged from 10 to 100 mg L -1 . Meanwhile, chlorophyll contents were decreased, the chloroplasts were swollen, and thylakoids were disorganized under all Fe treatments. Iron-based priming significantly enhanced SOD, POD, and CAT activities in Kobresia roots. In conclusion, the thick cuticle-covered seed coat of K. capillifolia postponed the penetration of FeNPs into seeds, so FeNPs priming had a weak impact on seed germination. The sustainable release of Fe ions from FeNPs and the uptake of Fe ions by roots affected the physiology, biochemistry and morphology of K. capillifolia. The findings of this study provide an in-depth understanding of how FeNPs impact the alpine meadow plant, K. capillifolia., 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 Masson SAS. All rights reserved.)

Nanomaterials at the neural interface can provide the bridge between bioelectronic devices and native neural tissues and achieve bidirectional transmission of signals with our brain. Photoactive nanomaterials, such as inorganic and polymeric nanoparticles, nanotubes, nanowires, nanorods, nanosheets or related, are being explored to mimic, modulate, control, or even substitute the functions of neural cells or tissues. They show great promise in next generation technologies for the neural interface with excellent spatial and temporal accuracy. In this review, we highlight the discovery and understanding of these nanomaterials in precise control of an individual neuron, biomimetic retinal prosthetics for vision restoration, repair or regeneration of central or peripheral neural tissues, and wireless deep brain stimulation for treatment of movement or mental disorders. The most intriguing feature is that the photoactive materials fit within a minimally invasive and wireless strategy to trigger the flux of neurologically active molecules and thus influences the cell membrane potential or key signaling molecule related to gene expression. In particular, we focus on worthy pathways of photosignal transduction at the nanomaterial-neural interface and the behavior of the biological system. Finally, we describe the challenges on how to design photoactive nanomaterials specific to neurological disorders. There are also some open issues such as long-term interface stability and signal transduction efficiency to further explore for clinical practice.

Infection-induced chronic wounds cause prolonged pains, a high risk of amputation, and even increased mortality in immunocompromised patients. Here we report an antibacterial microneedle (MN) patch, which features high degradability in biological fluids and gelatinase-responsive release of an antibacterial photothermal peptide AMP-Cypate. We first synthesize gelatin nanoparticles (GNPs) and then conjugate the AMP-Cypate to afford composite AMP-Cypate@GNPs. The proteinaceous nanoparticles can responsively release AMP-Cypate in the presence of gelatinase, an enzyme secreted specifically by Staphylococcus aureus (S. aureus). AMP-Cypate@GNPs were then deposited in the tips of MNs fabricated by PVP and recombinant human type III collagen (Col III) to devise the antibacterial MN/AMP-Cypate@GNP patches. When applied to the infection site, MNs break through the epidermis and the stratum corneum, dissolve in the infected dermis, reach the bacterial colony or biofilm, release AMP-Cypate@GNPs, and exert a gelatinase-responsive photothermal therapy under near-infrared (NIR) irradiation to kill the pathogen S. aureus. In a rat model of staphylococcal infection-induced chronic wounds mimicking the condition of diabetic foot ulcer, the antibacterial MN/AMP-Cypate@GNP patches eradiated the bacterial infection and resulted in complete healing of the wounds, proving its potential application in the treatment of chronic wound infections and diabetic foot ulcers., (Copyright © 2022. Published by Elsevier B.V.)

Nitrate (NO 3 - ) is a type of common pollutant in aqueous systems. Electrochemical NO 3 - reduction is an ecofriendly and sustainable strategy, which can selectively reduce NO 3 pollutants at the same time. In this work, Co nanoparticles decorated corncob-derived biomass carbon as a highly active electrocatalyst for NO - to highly value-added NH 3 and remove NO 3 - pollutants at the same time. In this work, Co nanoparticles decorated corncob-derived biomass carbon as a highly active electrocatalyst for NO 3 - to NH 3 conversion. Such a catalyst can achieve an amazing Faradaic efficiency of 93.4% and a large NH 3 yield of 0.60 mmol h -1 cm -2 in alkaline media. 15 N-Labeling experiment proves that the detected NH 3 is derived from NO 3 - electroreduction. In addition, it also displays excellent durability in long-term and cycle-electrolysis tests.

In the present study, we investigate the combined interaction of mesoporous silica (SiO 2 ) and photocatalytic titanium dioxide (TiO 2 ) nanoparticles with lipid membranes, using neutron reflectometry (NR), cryo-transmission electron microscopy (cryo-TEM), fluorescence oxidation assays, dynamic light scattering (DLS), and ζ-potential measurements. Based on DLS, TiO 2 nanoparticles were found to display strongly improved colloidal stability at physiological pH of skin (pH 5.4) after incorporation into either smooth or spiky ("virus-like") mesoporous silica nanoparticles at low pH, the latter demonstrated by cryo-TEM. At the same time, such matrix-bound TiO 2 nanoparticles retain their ability to destabilize anionic bacteria-mimicking lipid membranes under UV-illumination. Quenching experiments indicated both hydroxyl and superoxide radicals to contribute to this, while NR showed that free TiO 2 nanoparticles and TiO 2 loaded into mesoporous silica nanoparticles induced comparable effects on supported lipid membranes, including membrane thinning, lipid removal, and formation of a partially disordered outer membrane leaflet. By comparing effects for smooth and virus-like mesoporous nanoparticles as matrices for TiO 2 nanoparticles, the interplay between photocatalytic and direct membrane binding effects were elucidated. Taken together, the study outlines how photocatalytic nanoparticles can be readily incorporated into mesoporous silica nanoparticles for increased colloidal stability and yet retain most of their capacity for photocatalytic destabilization of lipid membranes, and with maintained mechanisms for oxidative membrane destabilization. As such, the study provides new mechanistic information to the widely employed, but poorly understood, practice of loading photocatalytic nanomaterials onto/into matrix materials for increased performance.

Aim: To formulate and assess the anticancer effect of the poly(lactic-co-glycolic acid) (PLGA) copolymer with the thioether groups (diethyl sulfide [Des]) and disulfide bond (cystamine containing disulfide [Cys]), which encapsulated the anticancer drug paclitaxel (PTX) and triggered PTX release in cancer cell H 2 O 2 -rich or glutathione-rich surroundings. Methods: PLGA- b -P (Des@Cys) and PLGA- b -P nanoparticles loaded with PTX were prepared and characterized in vitro . The delivery ability of the PLGA- b -P nanoparticles and PLGA- b -P-PTX nanoparticles was assessed on a CT26 (mouse colon cancer cell line) and mouse lung cancer LLC model. Results: The nanoparticles were successfully prepared. Compared with free PTX, the formulated PLGA- b -P nanoparticles loaded with PTX exhibited greater accumulation at the tumor site in the mouse model. Conclusion: PLGA- b -P nanoparticles promote drug accumulation at tumor sites, providing an effective strategy for an intelligent, responsive drug-delivery system.

Achieving molecular sample capture at micro/nanoscales while integrating functions of controllable loading and real-time monitoring of cargo molecules is of great significance in the development of intelligent micro/nanorobots. Herein, we prepare a temperature-responsive microsampling nanorobot by encapsulating metal (Au) nanodots inside hollow mesoporous silica nanoparticles and grafting a temperature-responsive polymer, poly( N -isopropylacrylamide), on their external surface. The molecular gate of nanochannels accessing the internal hollow reservoir can be switched between "open" and "closed" states by regulating the temperature, allowing on-demand loading and releasing of small molecules. The internally embedded surface-enhanced Raman scattering hotspots of gold nanodots can serve as sensing probes for real-time detection of the molecular cargo load inside the hollow nanorobots. Furthermore, we demonstrate temperature-dependent self-propulsion behavior of the nanorobots driven by enzymatic reactions. The active motion behavior can favorably regulate the loading efficiency of molecular cargos. In addition, by further introducing the magnetic component Ni, the nanorobots can accomplish effective transportation of cargo molecules by magnetic guidance under real-time Raman monitoring. The current strategy is expected to provide a manipulable nanorobot platform for precise biomedical sampling, which holds promising potential for disease diagnosis or controlled drug delivery in precision medicine.

Cellulose nanomaterials, such as cellulose nanocrystals (CNCs), have received enormous attention in various material research fields due to their unique properties and green/sustainable nature, among other qualities. Herein, we report hollow-type annular cellulose nanocrystals (HTA-CNCs), which are generated by following a high-intensity ultrasonic treatment. The advanced aberration-corrected transmission electron microscopy results reveal that HTA-CNCs exhibit ring structures with a typical diameter of 10.0-30.0 nm, a width of 3.0-4.0 nm, and a thickness of 2.0-5.0 nm, similar to those of elementary crystallites. The X-ray diffraction measurements show that the as-prepared HTA-CNCs maintain the cellulose I structure. The changes in structure and hydrogen-bonding characteristics of HTA-CNCs are further determined based on the FT-IR results after deconvolution fitting, showing that three types of hydrogen bonds decrease and the content of free OH increases in HTA-CNCs compared with those in the original CNCs. Furthermore, molecular dynamics simulation is carried out to support the experimental study. The formation of HTA-CNCs might be attributed to the structural change and entropy increase. The hollow-type annular CNCs may have broad value-added applications as cellulose nanomaterials in different fields.

Meticulous surface patterning of nanoparticles with anisotropic patches as analogs of functional groups offers fascinating potential in many fields, particularly in controllable materials assembly. However, patchy colloids generally evolve into high-symmetry solid structures, mainly because the assembly interactions arise between patches via patch-to-patch recognition. Here, we report an assembly concept, that is, a soft patch, which enables selective and directional fusion of liquid droplets for producing highly asymmetrical hollow nanospacecrafts. Our approach enables precise control of hollow nanoparticle diameters by manipulating droplet fusion regions. By controlling the patch number, more orientations are accessible to droplet fusion, allowing for increased degrees of complexity of hollow self-assemblies. The versatility and curvature-selective growth of this strategy are demonstrated on three nonspherical nanoparticles, enabling the creation of highly asymmetric nanospacecrafts. By patterning Au-core Ag-shell nanorods, the nanospacecraft can be programmed in response to either H 2 O 2 or near-infrared light, exhibiting dual-mode response behavior with a 208% increase in the diffusion coefficient in both modes compared with other nanoscale low-asymmetry active materials. Overall, these findings are a significant step toward designing new patch interactions for materials self-assembly for creating complex hollow colloids and functional nanodevices that are otherwise inaccessible.

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis., (© 2022. The Author(s).)

It is generally considered that photoacoustic imaging (PAI) and fluorescence imaging (FLI) cannot be enhanced concurrently, as they are dependent on competitive photophysical processes at the single-molecule level. Herein, we reveal that BDTR9-OC8 and BDTR9-C8, which have identical π-conjugated backbones but are substituted by side chains of different rigidity, show distinct phototheranostic properties in the aggregated state. The NIR-II FLI and PAI brightness of BDTR9-C8 nanoparticles are enhanced by 4.6 and 1.4 times compared with BDTR9-OC8 nanoparticles. Theoretical calculations and GIWAXS analysis revealed that BDTR9-C8 with rigid side chains shows a relative amorphous condensed state, which will benefit the efficient transportation of photo-generated excitons and phonons, subsequently enhancing the FLI and PAI signals. Besides, both nanoparticles exhibit excellent photothermal conversion efficiency due to their strong light-harvesting capability and are considered effective photothermal therapy materials. This work provides an illuminating strategy for material design in the future., (© 2022 Wiley-VCH GmbH.)

As a traditional treatment for papillary thyroid cancer (PTC), surgical resection of diseased tissues often brings lots of inconveniences to patients, and the tumor recurrence and metastasis are difficult to avoid. Herein, we developed a gene and photothermal combined therapy nanosystem based on a polypyrrole (Ppy)-poly(ethylene imine)-siILK nanocomplex (PPR ILK ) to achieve minimally invasive ablation and lymphatic metastasis inhibition in PTC simultaneously. In this system, gelatin-stabilized Ppy mainly acted as a photothermal- and photoacoustic (PA)-responsive nanomaterial and contributed to its well-behaved photosensitivity in the near-infrared region. Moreover, gelatin-stabilized Ppy possessed a charge reversal function, facilitating the tight conjunction of siILK gene at physiological pH (7.35-7.45) and its automatic release into acidic lysosomes (pH 4.0-5.5); the proton sponge effect generated during this process further facilitated the escape of siILK from lysosomes to the cytoplasm and played its role in inhibiting PTC proliferation and lymphatic metastasis. With the guidance of fluorescence and PA bimodal imaging, gene delivery and Ppy location in tumor regions could be clearly observed. As a result, tumors were completely eradicated by photothermal therapy, and the recurrences and metastases were obviously restrained by siILK.

Reduction of soluble Cr(VI) into insoluble Cr(III) by iron sulfide (FeS) minerals under anoxic conditions has been widely observed in natural and engineered systems. Yet, information has been lacking on the FeS-mediated oxidation and remobilization potential of Cr(III) under varying environmental conditions. The objective of this study was to investigate FeS-mediated redox transformation of Cr(III) to Cr(VI) and the associated mobilization and immobilization when Cr(III)-FeS systems are exposed to atmospheric conditions. The results showed that FeS nanoparticles facilitated rapid and strong Fenton-like reactions during the early-stage oxygenation of FeS, resulting in rapid production of hydroxyl radicals (•OH). Consequently, Cr(III) was rapidly oxidized into Cr(VI). Yet, as the reactions proceeded, the oxidative potential was counteracted by competitive scavenging of •OH by Fe(II) and S(-II) from FeS and the reduction reactions by these electron donors. At equilibrium, all Cr(VI) was reduced back to Cr(III) at an FeS-Cr(III) molar ratio of 10:1, while a small fraction of Cr(VI) persisted in solid products of Cr(OH) 3 (s) at an FeS-Cr(III) molar ratio of 1:1. Acidic conditions favored the generation of Cr(VI) and the equilibrium concentration of Cr(VI) in oxic FeS NPs systems at pH 5.0 was 1.7 times higher than at pH 9.0. Overall, the FeS-induced Fenton-like reactions and the oxidation of Cr(III) were favored in the early stage, but quenched in the later stage and outcompeted by the reduction of Cr(VI) if sufficient FeS was available. The findings provide new insights into the hydrochemical processes that can affect the speciation, toxicity, and mobility of Cr in aquatic systems containing FeS and Cr., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Intracellular bacteria in latent or dormant states tolerate high-dose antibiotics. Fighting against these opportunistic bacteria has been a long-standing challenge. Herein, the design of a cascade-targeting drug delivery system (DDS) that can sequentially target macrophages and intracellular bacteria, exhibiting on-site drug delivery, is reported. The DDS is fabricated by encapsulating rifampicin (Rif) into mannose-decorated poly(α-N-acryloyl-phenylalanine)-block-poly(β-N-acryloyl-d-aminoalanine) nanoparticles, denoted as Rif@FAM NPs. The mannose units on Rif@FAM NPs guide the initial macrophage-specific uptake and intracellular accumulation. After the uptake, the detachment of mannose in acidic phagolysosome via Schiff base cleavage exposes the d-aminoalanine moieties, which subsequently steer the NPs to escape from lysosomes and target intracellular bacteria through peptidoglycan-specific binding, as evidenced by the in situ/ex situ co-localization using confocal, flow cytometry, and transmission electron microscopy. Through the on-site Rif delivery, Rif@FAM NPs show superior in vitro and in vivo elimination efficiency than the control groups of free Rif or the DDSs lacking the macrophages- or bacteria-targeting moieties. Furthermore, Rif@FAM NPs remodel the innate immune response of the infected macrophages by upregulating M1/M2 polarization, resulting in a reinforced antibacterial capacity. Therefore, this biocompatible DDS enabling macrophages and bacteria targeting in a cascade manner provides a new outlook for the therapy of intracellular pathogen infection., (© 2022 Wiley-VCH GmbH.)

The synergetic photodynamic/photothermal therapy, activated via a single-second near-infrared (NIR-II) laser and guided by photoacoustic imaging (PAI), receives significant attention for precise in vivo therapy. However, due to the lack of a corresponding theranostic agent, it faces a great challenge for practical clinical implementation. Here, we present a single diagnostic and therapeutic nanoplatform named carbon nitride nanoparticles (CN-NPs) for efficient NIR-II PAI-guided photodynamic therapy (PDT)/photothermal therapy (PTT). The CN-NPs were obtained by incorporating an aromatic compound (PTCDA) with a large π-structure into melem by high-temperature polymerization. The absorption of the obtained CN-NPs was significantly enhanced compared with pristine melem. Under 1064 nm laser illumination, sufficient reactive oxygen species (ROS) generated by CN-NPs could reduce the mitochondrial membrane potential. Moreover, the CN-NPs exhibited an efficient PTT effect through improved photothermal stability and high photo-to-heat conversion efficiency (47.6%). We were also able to monitor the accumulation and metabolism of CN-NPs in vivo of mice in real time using PAI. The in vivo experiments proved that the CN-NPs could inhibit tumor growth and recurrence completely under 1064 nm. Thus, the proposed innovative strategy would open a new avenue to explore and construct NIR-II responsive nanoplatforms with enhanced performance and safety for multimodal phototheranostics.

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (d avg = 1.76 nm). Higher positive (brighter or T 1 ) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T 1 MRI contrast agents in tumor imaging via GlcN effects.

Spherical nucleic acid (SNA), as a good gene delivery system, has a good application prospect for transdermal administration in skin disorder treatment. However, most of the traditional SNA core materials are non-degradable materials, so it is worthy of further research. Herein, we report a spherical nucleic acid based on poly-hyaluronic acid (PHA) for the co-delivery of a typical chemotherapeutic drug, doxorubicin (DOX), and an antisense oligonucleotide (ASO) against the tissue inhibitor of metalloproteinases 1 (TIMP-1) for the treatment of hypertrophic scars (HS) which are caused by abnormal fibroblast proliferation. Our study showed that PHA-based SNAs simultaneously bearing TIMP-1 ASO and DOX (termed PHAAD) could significantly promote skin penetration, improve the cellular uptake, and effectively down-regulate the TIMP-1 expression and enhance the cytotoxicity of DOX. Moreover, PHAAD nanoparticles facilitated the apoptosis of hypertrophic scar cells, and reduced the burden and progression of hypertrophic scars in a xenografted mouse model without adverse side effects. Thus, our PHA-based SNA represents a new transdermal delivery vehicle for efficient combinatorial chemo and gene therapy, which is expected to treat various skin disorders.

Malignant pleural effusion (MPE) is indicative of terminal malignancy with a uniformly fatal prognosis. Often, two distinct compartments of tumour microenvironment, the effusion and disseminated pleural tumours, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumour-associated myeloid cells with the tumour-promoting phenotype, impairing antitumour immunity. Here we developed a liposomal nanoparticle loaded with cyclic dinucleotide (LNP-CDN) for targeted activation of stimulators of interferon genes signalling in macrophages and dendritic cells and showed that, on intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both effusion and pleural tumours. Moreover, combination immunotherapy with blockade of programmed death ligand 1 potently reduced MPE volume and inhibited tumour growth not only in the pleural cavity but also in the lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Thermally activated delayed fluorescence (TADF) materials with extremely small singlet-triplet energy offsets have opened new horizons for the development of metal-free photosensitizers for photodynamic therapy (PDT) in recent years. However, the exploration of near-infrared (NIR) TADF emitters for efficient two-photon-excited (TPE) PDT is still a formidable challenge, thus it has not been reported yet. In this study, purely organic photosensitizers (PSs) based on the TADF nanoparticles (NIR-TADF NPs) are designed for efficient TPE-PDT, which show excellent singlet oxygen generation ability. Thanks to the intrinsic two-photon excitation and NIR emission characteristics, the NIR-TADF NPs demonstrate promising potential in both single-photon-excited (SPE) and TPE NIR imaging. More importantly, the anti-tumor efficiency and biosafety of TADF-based PSs at the small animal level are confirmed in A549 tumor xenograft models under TPE laser irradiance, which will facilitate the practical biomedical applications of TADF materials. This work not only provides a promising strategy to develop metal-free PSs, but also expands the applied scope of TADF-based nanotherapeutics and advances their possible clinical translation in cancer therapy., (© 2022 Wiley-VCH GmbH.)

Nanoplastics (NPs) pollution of aquatic systems is becoming an emerging environmental issue due to their stable structure, high mobility, and easy interactions with ambient contaminants. Effective removal technologies are urgently needed to mitigate their toxic effects. In this study, we systematically investigated the removal effectiveness and mechanisms of a commonly detected nanoplastics, carboxyl-modified polystyrene (PS-COOH) via coagulation and sedimentation processes using aluminum chloride (AlCl 3 ) as a coagulant. PS-COOH appeared as clearly defined and discrete spherical nanoparticles in water with a hydrodynamic diameter of 50 nm. The addition of 10 mg/L AlCl 3 compressed and even destroyed the negatively charged PS-COOH surface layer, decreased the energy barrier, and efficiently removed 96.6% of 50 mg/L PS-COOH. The dominant removal mechanisms included electrostatic adsorption and intermolecular interactions. Increasing the pH from 3.5 to 8.5 sharply enhanced the PS-COOH removal, whereas significant loss was observed at pH 10.0. High temperature (23 °C) favored the removal of PS-COOH compared to lower temperature (4 °C). High PS-COOH removal efficiency was observed over the salinity range of 0 - 35‰. The presence of positively charged Al 2 O 3 did not affect the PS-COOH removal, while negatively charged SiO 2 reduced the PS-COOH removal from 96.6% to 93.2%. Moreover, the coagulation and sedimentation process efficiently removed 90.2% of 50 mg/L PS-COOH in real surface water even though it was rich in inorganic ions and total organic carbon. The fast and efficient capture of PS-COOH by AlCl 3 via a simple coagulation and sedimentation process provides a new insight for the treatment of NPs from aqueous environment., (Copyright © 2021. Published by Elsevier Ltd.)

Prodrug nanoassemblies have emerged as a promising platform for the delivery of anticancer drugs. PEGylation is a "gold standard" to improve colloidal stability and pharmacokinetics of nanomedicines. However, the clinical application of PEG materials is challenged by in vivo oxidative degradation and immunogenicity. Rational design of advanced biomaterials for the surface modification of nanomedicines is the hot spot of research. Here, a zwitterionic sulfobetaine surfactant is constructed as a novel surface modifier to coassemble with 10-hydroxycamptothecin-linoleic acid conjugate, with the classical PEGylated material as control. Interestingly, both the type and ratio of surfactants have profound impacts on the molecular mechanisms of the assembly of prodrugs, thereby affecting the pharmaceutical properties. Compared with PEGylated spherical prodrug nanoassemblies, zwitterion-modified prodrug nanoassemblies have distinct rod shape and superhydrophilic surface, and exhibit potent antitumor activity due to the combination of multiple advantages in terms of colloidal stability, cellular uptake, and pharmacokinetics. The findings illustrate the crucial role of zwitterionic surfactants as the surface modifier in the determination of in vivo fate of the prodrug nanoassemblies, and pave the way for the development of advanced nanomedicines., (© 2021 Wiley-VCH GmbH.)

Triple negative breast cancer (TNBC) is the most dangerous subtype of breast cancer accompanying by unfavorable prognosis due to lack of specific therapeutic targets. Paclitaxel (PTX) is the first-line chemotherapeutic drug for TNBC and niclosamide (NLM) was identified as an inhibitor for TNBC and breast cancer stem cells (BCSCs). Intratumoral drug delivery system was a hopeful alternative for chemotherapeutic drug administration due to its targeting efficiency with lower systemic toxicity. Herein, an injectable PTX nanocrystals (PTX-NCs) and NLM nanocrystals (NLM-NCs) co-loaded PLGA-PEG-PLGA thermosensitive hydrogel (PNNCs-Ts Gel) was designed for TNBC intratumoral treatment. The final formulation realized high drug loading and appropriate particle size. PNNCs-Ts Gel displayed sustained drug release for up to 8 days in vitro. In vitro antitumor tests observed synergetic effects of combined therapy in terms of inhibiting cell proliferation and migration, inducing apoptosis. In vivo combined therapy presented a tumor growth inhibition rate about 68.8% and desired safety. Moreover, tumors after PNNCs-Ts Gel intratumoral injection possessed the lowest ratio of BCSCs, exhibiting this formulation had good ability in suppressing BCSCs and therefore could possibly prevent TNBC recurrence and metastasis. These results suggested that PNNCs-Ts Gel could be a promising strategy for TNBC treatment., (Copyright © 2021. Published by Elsevier B.V.)