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In the process of tumor metastasis, tumor cells can acquire invasion by excessive uptake of nutrients and energy and interact with the host microenvironment to shape a premetastatic niche (PMN) that facilitates their colonization and progression in the distal sites. Pyruvate is an essential nutrient that engages in both energy metabolism and remodeling of the extracellular matrix (ECM) in the lungs for PMN formation, thus providing a target for tumor metastasis treatment. There is a paucity of strategies focusing on PMN prevention, which is key to metastasis inhibition. Here, we design a bioresponsive nanoparticle (HP/GU) based on a disulfide-cross-linked hyperbranched polyethylenimine (D-PEI) core and a hyaluronic acid (HA) shell with a reactive oxygen species (ROS)-sensitive cross-linker between them to encapsulate glucose oxidase (GOX) and a mitochondrial pyruvate carrier (MPC) inhibitor via electrostatic interaction, which reinforces starvation therapy and reduces PMN formation in the lungs via inhibiting pyruvate metabolism. In tumor cells, GOX and MPC inhibitors can be rapidly released and synergistically reduce the energy supply of tumor cells by consuming glucose and inhibiting pyruvate uptake to decrease tumor cell invasion. MPC inhibitors can also reduce ECM remodeling by blocking cellular pyruvate metabolism to prevent PMN formation. Consequently, HP/GU achieves an efficient inhibition of both primary and metastatic tumors and provides an innovative strategy for the treatment of tumor metastases.

Lanthanide-doped upconversion nanoparticles (Ln-UCNPs) have been considered promising materials for various fields, such as biomedical and industrial applications. However, data and reports regarding its toxicity and environmental risks are scarce. Under these circumstances, data must be obtained to fully understand potential toxicity and adverse outcome pathways. In the present study, the toxicity of uncoated Ln-UCNP cores (NaYF 4 :Yb, Er) was systematically assessed in zebrafish embryos during early developmental stages. Ln-UCNPs were found to have multiple toxic effects, such as effects on survival rates, delayed hatching times, shorter body lengths, altered heart rates and blood circulation (significantly reduced), and neurobehavioral impairments in response to photoperiod stimulation. Bioimaging showed that Ln-UCNPs were distributed on the chorion, eyes, and skin at 72 hpf. However, it accumulates in the pharynx, esophagus, and intestine after oral administration. Ln-UCNPs disrupt the diversity and abundance of host-associated microorganisms (gut microbiota) leading to an increase in the prevalence of harmful bacteria in zebrafish. Transcriptomic and Ingenuity Pathway Analysis (IPA) predicted Interleukin-8 (IL-8) signaling, neuroinflammation, cardiac hypertrophy signaling pathways, immune and inflammation-related response interferon-gamma (ifnγ), and miR-155 as key mediators in regulatory effects. Based on this, a causal network was built showing the strong links between the induced gene expression of differentially expressed genes (DEGs), such as nitric oxide synthase 2 (nos2) and tumor necrosis factor (tnf) upon Ln-UCNPs treatment, and with the downstream adverse outcomes, in particular, the promotion of apoptosis, liver damage, and inflammatory response. Finally, RT-qPCR analysis confirmed the up-regulated expression of nos2 and tnf in the exposed larvae, consistent with the observation of an increased number of fluorescence-labelled neutrophils and macrophages in lyz: DsRed transgenic zebrafish until 120 hpf exposure, which together demonstrated the proinflammatory effects of Ln-UCNPs on organisms. In conclusion, we illustrated the developmental toxicity, disruption of gut-microbiome, and proinflammatory effects of Ln-UCNP cores on zebrafish, and the causal network from IPA analysis may help further elucidate the adverse outcome pathway of Ln-UCNPs., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Atherosclerosis is a persistent inflammatory condition of the blood vessels associated with abnormalities in lipid metabolism. Development of biomimetic nanoplatforms provides an effective strategy. Herein, inspired by the peptide CLIKKPF spontaneously coupling to phosphatidylserine (PS) on the inner leaflet of cell membranes specifically, MM@NPs were constructed by macrophage membrane spontaneous encapsulation of cyclodextrin-based nanoparticles modified with the peptide CLIKKPF and loaded with the hydrophobic compound resveratrol. MM@NPs could be specifically phagocytized by the activated endothelium with the overexpressed VCAM-1 for enhancing target delivery into the pathological lesion. Additionally, for the ApoE -/- mice, MM@NPs provide comprehensive treatment efficiency in reducing oxidant stress, alleviating the inherent inflammation, and decreasing cholesterol deposition, subsequently resulting in the atherosclerotic plaque regression. Therefore, MM@NPs could be one possible candidate for improving lipid metabolism and inflammation in atherosclerosis.

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses., 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.)

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice., 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.)

Infections induced by Gram-positive bacteria pose a great threat to public health. Antibiotic therapy, as the first chosen strategy against Gram-positive bacteria, is inevitably associated with antibiotic resistance selection. Novel therapeutic strategies for the discrimination and inactivation of Gram-positive bacteria are thus needed. Here, a specific type of aggregation-induced emission luminogen (AIEgen) with near-infrared fluorescence emission as a novel antibiotic-free therapeutic strategy against Gram-positive bacteria is proposed. With the combination of a positively charged group into a highly twisted architecture, self-assembled AIEgens (AIE nanoparticles (NPs)) at a relatively low concentration (5 µm) exhibited specific binding and photothermal effect against living Gram-positive bacteria both in vitro and in vivo. Moreover, toxicity assays demonstrated excellent biocompatibility of AIE NPs at this concentration. All these properties make the AIE NPs as a novel generation of theranostic platform for combating Gram-positive bacteria and highlight their promising potential for in vivo tracing of such bacteria., (© 2024 Wiley‐VCH GmbH.)

Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors via removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion via reverse cholesterol transport but also scavenge the overaccumulated ROS. β-Cyclodextrin (β-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. β-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs in vivo circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.

Lignin, as a natural polyphenol, displays anti-oxidant activity by trapping and binding free radicals through its free phenolic hydroxyl groups. However, the most accessible form, industrial lignins, generally has low phenolic hydroxyl content, which severely limits their application value and scenarios. Herein, we showed that potassium-glycerate deep eutectic solvent (PG-DES) treatment can be combined with laccase oxidation to afford prepared high antioxidant lignin nanoparticles (HA-LNPs) with notably improved anti-oxidant activities benefiting from both the enhanced phenolic hydroxyl content 170.8 % and reduced average particle size (59.0 nm). At concentrations as low as 60 μg/mL, HA-LNPs showed favorable effects in promoting collagen formation. When HA-LNPs were used as an active ingredient in the anti-aging mask formulation, the reactive oxygen species (ROS) scavenging activity of mask samples containing 0.4 % HA-LNPs reached 37.2 %. The data suggest great promise of HA-LNPs as a natural antioxidant for formulating in anti-aging skin care products., 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.)

Atherosclerosis (AS), a pathological cause of cardiovascular disease, results from endothelial injury, local progressive inflammation, and excessive lipid accumulation. AS plaques rich in foam cells are prone to rupture and form thrombus, which can cause life-threatening complications. Therefore, the assessment of atherosclerotic plaque vulnerability and early intervention are crucial in reducing the mortality rates associated with cardiovascular disease. In this work, A fluorescent probe FC-TPA was synthesized, which switches the fluorescence state between protonated and non-protonated, reducing background fluorescence and enhancing imaging signal-to-noise ratio. On this basis, FC-TPA is loaded into cyclodextrin (CD) modified with phosphatidylserine targeting peptide (PTP) and coated with hyaluronic acid (HA) to construct the intelligent responsive diagnostic nanoplatform (HA@PCFT). HA@PCFT effectively targets atherosclerotic plaques, utilizing dual targeting mechanisms. HA binds strongly to CD44, while PTP binds to phosphatidylserine, enabling nanoparticle aggregation at the lesion site. ROS acts as a smart release switch for probes. Both in vitro and in vivo evaluations confirm impressive lipid-specific fluorescence imaging capabilities of HA@PCFT nanoparticles (NPs). The detection of lipid load in atherosclerotic plaque by fluorescence imaging will aid in assessing the vulnerability of atherosclerotic plaque. STATEMENT OF SIGNIFICANCE: Currently, numerous fluorescent probes have been developed for lipid imaging. However, some challenges including inadequate water solubility, nonspecific distribution patterns, and fluorescence background interference, have greatly limited their further applications in vivo. To overcome these limitations, a fluorescent molecule has been designed and synthesized, thoroughly investigating its photophysical properties through both theoretical and experimental approaches. Interestingly, this fluorescent molecule exhibits the reversible fluorescence switching capabilities, mediated by hydrogen bonds, which effectively mitigate background fluorescence interference. Additionally, the fluorescent molecules has been successfully loaded into nanocarriers functionalized with the active targeting abilities, which has significantly improved the solubility of the fluorescent molecules and reduced their nonspecific distribution in vivo for an efficient target imaging in atherosclerosis. This study provides a valuable reference for evaluating the performance of such fluorescent dyes, and offers a promising perspective on the design of the target delivery systems for atherosclerosis., 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 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Current treatment options for diabetic wounds face challenges due to low efficacy, as well as potential side effects and the necessity for repetitive treatments. To address these issues, we report a formulation utilizing trisulfide-derived lipid nanoparticle (TS LNP)-mRNA therapy to accelerate diabetic wound healing by repairing and reprogramming the microenvironment of the wounds. A library of reactive oxygen species (ROS)-responsive TS LNPs was designed and developed to encapsulate interleukin-4 (IL4) mRNA. TS2-IL4 LNP-mRNA effectively scavenges excess ROS at the wound site and induces the expression of IL4 in macrophages, promoting the polarization from the proinflammatory M1 to the anti-inflammatory M2 phenotype at the wound site. In a diabetic wound model of db/db mice, treatment with this formulation significantly accelerates wound healing by enhancing the formation of an intact epidermis, angiogenesis, and myofibroblasts. Overall, this TS LNP-mRNA platform not only provides a safe, effective, and convenient therapeutic strategy for diabetic wound healing but also holds great potential for clinical translation in both acute and chronic wound care., Competing Interests: Competing interests statement:Y.D. is a scientific advisory board member and holds equity in Arbor Biotechnologies and Sirnagen Therapeutics. Y.D. is a co-founder and holds equity in Immunanoengineering Therapeutics. Other authors declare no conflict of interest. A patent application related to this work was filed by The Ohio State University.

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu 2+ ) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu 2+ was reduced to Cu + by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H 2 O 2 ) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.

Oral insulin therapies targeting the liver and further simulating close-looped secretion face significant challenges due to multiple trans-epithelial barriers. Herein, ursodeoxycholic acid (UDCA)-decorated zwitterionic nanoparticles (NPs) (UC-CMs@ins) are designed to overcome these barriers, target the liver, and respond to glycemia, thereby achieving oral one-time-per-day therapy. UC-CMs@ins show excellent mucus permeability through the introduction of zwitterion (carboxy betaine, CB). Furthermore, UC-CMs@ins possess superior cellular internalization via proton-assisted amino acid transporter 1 (PAT1, CB-receptor) and apical sodium-dependent bile acid transporter (ASBT, UDCA-receptor) pathways. Moreover, UC-CMs@ins exhibit excellent endolysosomal escape ability and improve the basolateral release of insulin into the bloodstream via the ileal bile acid-binding protein and the heteromeric organic solute transporter (OSTα- OSTβ) routes compared with non-UDCA-decorated C-CMs@ins. Therefore, CB and UDCA jointly overcome mucus and intestinal barriers. Additionally, UC-CMs@ins prevent insulin degradation in the gastrointestinal tract for crosslinked structure, improve insulin accumulation in the liver for UDCA introduction, and effectively regulate glycemia for "closed-loop" glucose control. Surprisingly, oral ingestion of UC-CMs@ins shows a superior effect on glycemia (≈22 h, normoglycemia) and improves postprandial glycemic levels in diabetic mice, illustrating the enormous potential of the prepared NPs as a platform for oral insulin administration in diabetes treatment., (© 2024 Wiley-VCH GmbH.)

Cancers remain the leading cause of mortality worldwide. It is crucial to detect cancer at an early stage for improving survival rates. Biomarkers have precise implications for cancer progression. Here, we built a straightforward DNA probe system that could be activated by near-infrared light to detect dual miRNAs with a high specificity. This probe is built on the basis of upconversion nanoparticles, which could emit ultraviolet light and activate DNA probes adsorbed on the outer layer. The DNA probe system is remotely controlled through manipulation of the near-infrared (NIR) light, enabling simultaneous detection of dual miRNAs. The DNA nanosystem could be effectively endocytosed by cancer cells and reflect expression levels of dual miRNAs. Overall, this study demonstrates a promising remote-controlled DNA nanoplatform for the simultaneous detection of dual miRNAs, which has tremendous potential for precise cancer diagnostics and therapies.

The aim of this study was to enhance the dissolution rate and oral bioavailability of herpetetrone (HPT) by preparing nanosuspensions (NSs) and evaluate the changes in its anti-hepatic fibrosis effect. Herpetetrone nanosuspension (HPT-NS) was prepared using the ultrasound-precipitation technique, and characterised on the basis of mean diameter, zeta potential (ZP), encapsulation efficiency percent (EE%), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD). In addition, the pharmacokinetics and anti-hepatic fibrosis activity were evaluated. HPT-NS prepared with the optimised formulation was found to be spherical with mean diameter of 177.48 ± 6.13 nm, polydispersity index (PDI) of 0.108 ± 0.002 and ZP of -17.28 ± 2.02 mV. The EE (m/m, %) was 83.25 ± 0.27. XRPD analyses confirmed that the amorphous state of HPT in HPT-NS remained unchanged. The dissolution rate of HPT-NS was significantly higher than that of HPT coarse suspensions (HPT-CSs). Following oral administration, C max and AUC 0- t of HPT-NS showed a significant increase ( p  < 0.05). In vitro , HPT inhibited the proliferation of HSC-T6 cells and induced apoptosis by up-regulating the expression of Bax proteins and down-regulating the expression of Bcl-2 and TGF-β1 proteins. Compared with HPT-CS, HPT-NS exhibited a more pronounced anti-fibrotic effect. HPT-NS, as a new drug formulation designed to improve the solubility and bioavailability of the drug, shows promising potential in enhancing the anti-liver fibrosis effect.

Aim: This study focused on treating periodontitis with bacterial infection and local over accumulation of reactive oxygen species. Materials & methods: Polydopamine nanoparticles (PDA NPs) were exploited as efficient carriers for encapsulated metronidazole (MNZ). The therapeutic efficacy and biocompatibility of PDA@MNZ NPs were investigated through both in vitro and in vivo studies. Results: The nanodrug PDA@MNZ NPs were successfully fabricated, with well-defined physicochemical characteristics. In vitro , the PDA@MNZ NPs effectively eliminated intracellular reactive oxygen species and inhibited the growth of Porphyromonas gingivalis . Moreover, the PDA@MNZ NPs exhibited synergistic therapy for periodontitisin in vivo . Conclusion: PDA@MNZ NPs were confirmed with exceptional antimicrobial and antioxidant functions, offering a promising avenue for synergistic therapy in periodontitis.

Background: Accurate, sensitive, and rapid identification of leukemia cells in blood and bone marrow is of paramount significance for clinical diagnosis. An integrative technique combining traditional cytomorphology with immunophenotyping was proposed to improve the diagnostic efficiency in leukemia. On account of high photostability, biocompatibility, and signal-to-background ratio, upconversion nanoparticles (UCNPs) as luminescent labels have drawn substantial research scrutiny in immunolabeling., Methods: To achieve simultaneous determination, NaYF 4 :Yb,Er UCNPs were coupled with CD38 antibodies to construct immunofluorescence probes that were developed to bind to diffuse large B cell lymphoma (DLBCL) cells, followed by Wright's staining that has been widely used in clinical work for morphological diagnosis. Further, the experimental conditions were optimized, such as medium, slice-making method, antibody dosage, incubation time, etc., Results: The cell morphology and immunolabeling could be observed simultaneously, and its simple operation rendered it a possibility for clinical diagnosis. The developed immunolabeling assay could achieve DLBCL cell counting with high reproducibility and stability, and the detection limit was as low as 1.54 cell/slice (>3 σ/s). Moreover, the proposed method also realized real blood and bone marrow sample analysis, and the results were consistent with the clinical diagnosis., Conclusion: Overall, this strategy can be carried out after simple laboratory training and has prospective biomedical applications in leukemia classification, diagnosis validation, and differential diagnostics., Competing Interests: Dr Fei Gao reports a pending patent “Accurate diagnosis of leukemia cells based on rare earth nanomaterial immunolabeling technology combined with cell morphology technology”. The authors declare that they have no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Chen et al.)

Glioblastoma multiforme (GBM) is the most common malignant brain tumor with low survival, primarily due to the blood-brain barrier (BBB) and high infiltration. Upconversion nanoparticles (UCNPs)-based near-infrared (NIR) phototherapy with deep penetration is a promising therapy method against glioma but faces low photoenergy utilization that is induced by spectral mismatch and single-site Förster resonance energy transfer (FRET). Herein, we designed a brain-targeting NIR theranostic system with a dual-site FRET route and superior spectral matching to maximize energy utilization for synergistic photodynamic and photothermal therapy of glioma. The system was fabricated by Tm-doped UCNPs, zinc tetraphenylporphyrin (ZnTPP), and copper sulfide (CuS) nanoparticles under multioptimized modulation. First, the Tm-doping ratio was precisely adjusted to improve the relative emission intensity at 475 nm of UCNPs (11.5-fold). Moreover, the J-aggregate of ZnTPP increased the absorption at 475 nm (163.5-fold) of monomer; both together optimize the FRET matching between UCNPs and porphyrin for effective NIR photodynamic therapy. Simultaneously, the emission at 800 nm was utilized to magnify the photothermal effect of CuS nanoparticles for photothermal therapy via the second FRET route. After being modified by a brain-targeted peptide, the system efficiently triggers the synergistic phototherapy ablation of glioma cells and significantly prolongs the survival of orthotopic glioma-bearing mice after traversing the BBB and targeting glioma. This success of advanced spectral modulation and dual-site FRET strategy may inspire more strategies to maximize the photoenergy utilization of UCNPs for brain diseases.

Microplastic and nanoplastic (MNP) pollution has become a major global food safety concern. MNPs can interact with food matrices, and their passage through the gastrointestinal tract can modify their properties. To explore whether and how food matrices influence MNP toxicity, we investigated the interactions between polystyrene nanoplastics (PS-NPs) and food matrices, using an in vitro gastrointestinal digestion model. Then, we tested cell viability, particle uptake and cellular toxicities induced by PS-NPs with food matrices in Caco-2 cells. The results showed that PS-NPs were aggregated, both with and without food matrices, after in vitro gastrointestinal digestion. Glyceryl trioleate exerted greater ability to stabilize digestas and to disperse PS-NPs than starch and bovine serum albumin. The protein corona's protein composition on PS-NPs varied when it interacted with different food matrices. Moreover, when combined with food matrices, the PS-NPs' uptake was enhanced, thus aggravating cellular inflammation, stress, and apoptosis levels. Finally, through co-exposure to a mixture of food matrices, we found a combined negative effect of PS-NPs and cadmium on cellular inflammation, stress, and apoptosis levels. This is the first study to compare the impact of various food matrices on the characteristics and cellular toxicities of ingested NPs in a simulated digestive tract., 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.)

Lipid nanoparticle (LNP)-formulated messenger RNA (mRNA) vaccineare a promising platform to prevent infectious diseases as demonstrated by the recent success of SARS-CoV-2 mRNA vaccines. To avoid immune recognition and uncontrolled inflammation, nucleoside-modified mRNA is used. However, such modification largely abrogates the innate immune responses that are critical to orchestrating robust adaptive immunity. Here we develop an LNP component-an adjuvant lipidoid-that can enhance the adjuvanticity of mRNA-LNP vaccines. Our results show that partial substitution of ionizable lipidoid with adjuvant lipidoid not only enhanced mRNA delivery, but also endowed LNPs with Toll-like receptor 7/8-agonistic activity, which significantly increased the innate immunity of the SARS-CoV-2 mRNA-LNP vaccine with good tolerability in mice. Our optimized vaccine elicits potent neutralizing antibodies against multiple SARS-CoV-2 pseudovirus variants, strong Th1-biased cellular immunity, and robust B cell and long-lived plasma cell responses. Importantly, this adjuvant lipidoid substitution strategy works successfully in a clinically relevant mRNA-LNP vaccine, demonstrating its translational potential., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Prodrug assembled nanoparticles integrate the merits of both prodrug and nanoparticle, which significantly improve pharmacokinetic parameters, enhance tumorous accumulation and decrease adverse effects, while they are challenged by disassembly upon dilution in blood, masking the superiority of nanoparticles (NPs). Herein, a reversibly "double locked" hydroxycamptothecin (HCPT) prodrug nanoparticle decorated with cyclic RGD peptide (cRGD) is developed for safe and efficient chemotherapy of orthotopic lung cancer in mice. HCPT prodrug is constructed from acetal (ace)-linked cRGD-PEG-ace-HCPT-ace-acrylate polymer, which is self-assembled into the nanoparticles with "the first lock" of HCPT. Then the nanoparticles undergo the in situ UV-crosslinking of the acrylate residues for constructing "the second lock" of HCPT. The obtained "double locked" nanoparticles (T-DLHN) with simple and well-defined construction are demonstrated to possess extremely high stability against 100-fold dilution and acid-triggered "unlock" including de-crosslinking and liberation of the pristine HCPT. In an orthotopic lung tumor of mouse model, T-DLHN reveals a prolonged circulation time of about 5.0 h, superb lung tumor-homing capacity with tumorous drug uptake of about 7.15%ID/g, resulting in significantly boosted anti-tumor activity and reduced adverse effects. Hence, these nanoparticles utilizing "double lock" and acid-triggered "unlock" strategies represent a unique and promising nanoplatform for safe and efficient drug delivery. STATEMENT OF SIGNIFICANCE: Prodrug assembled nanoparticles have the unique properties of the well-defined structure, systemic stability, improved pharmacokinetics, passive targeting and decreased adverse effects. However, prodrug assembled NPs would disassemble against extensive dilution in the blood circulation when intravenously injected into the body. Herein, we have designed a cRGD-directed reversibly "double-locked" HCPT prodrug nanoparticle (T-DLHN) for safe and efficient chemotherapy of orthotopic A549 human lung tumor xenografts. Upon intravenous injection, T-DLHN can overcome the shortcoming of disassembly against extensive dilution, prolong the circulation time due to the "double locked" configuration and then mediate targeted drug delivery into the tumors. After uptaken into the cells, T-DLHN undergoes concurrent de-crosslinking and liberation of HCPT under acidic condition for enhanced chemotherapeutic efficacy with negligible adverse effects., 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.)

The application of Epigallocatechin-3-gallate (EGCG) in food industry was limited by its low stability in aqueous solutions and poor bioavailability in vivo. The novel EGCG glycosylated arachin nanoparticles (Ara-CMCS-EGCG) and EGCG glycosylated casein nanoparticles (Cas-CMCS-EGCG) were prepared to improve the stability and bioavailability of EGCG. The effect of different variables on the storage stability and the slow-release behavior of novel glycosylation complexes in nanoparticle background solution and artificial gastrointestinal fluid were investigated. The results showed that the DPPH scavenging activity of Ara-CMCS-EGCG and Cas-CMCS-EGCG were stable in temperature (25 ∼ 70 °C). EGCG could enhance the crosslinking effect of molecular particles in glycosylation complexes solution. The glycosylated protein nanoparticles were stable to acid-base and enzymolysis in simulated gastrointestinal fluid. The release rate of EGCG in simulated intestinal fluid was higher than that in simulated gastric fluid. The glycosylated protein carrier can not only release EGCG slowly, but also significantly improve the stability and bioavailability of EGCG in simulated gastrointestinal fluid., 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.)

Ocular diseases seriously affect patients' vision and life quality, with a global morbidity of over 43 million blindness. However, efficient drug delivery to treat ocular diseases, particularly intraocular disorders, remains a huge challenge due to multiple ocular barriers that significantly affect the ultimate therapeutic efficacy of drugs. Recent advances in nanocarrier technology offer a promising opportunity to overcome these barriers by providing enhanced penetration, increased retention, improved solubility, reduced toxicity, prolonged release, and targeted delivery of the loaded drug to the eyes. This review primarily provides an overview of the progress and contemporary applications of nanocarriers, mainly polymer- and lipid-based nanocarriers, in treating various eye diseases, highlighting their value in achieving efficient ocular drug delivery. Additionally, the review covers the ocular barriers and administration routes, as well as the prospective future developments and challenges in the field of nanocarriers for treating ocular diseases., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Developing a hydrogel dressing with excellent antibacterial efficacy for accelerating wound healing is high desirable in clinical applications. In this work, NIR regulated metal-organic framework composite hydrogel dressing was constructed for enhanced antibacterial efficacy and accelerated wound healing via the compounding between hydrogel and UCNPs@ZrMOF-Pt nanoparticles. The visible light emitted from upconvertion nanoparticles (UCNPs) activated porphyrin based metal-organic framework (MOF) in composite hydrogel to generate 1 O 2 for photodynamic antibacterial therapy under NIR laser irradiation. Moreover, the UCNPs@ZrMOF-Pt in composite hydrogel with catalase-like performance could effectively convert the high concentration H 2 O 2 in wound to abundant O 2 , which relieved the hypoxic in infected wound. Thus, the photodynamic antibacterial efficacy was remarkably enhanced, leading to accelerate the wound healing. This work presented a novel strategy for high efficient antibacterial therapy and accelerated wound healing., 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.)

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics. Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT). Results: It is found that 10% Ce 3+ doped in the core and 100% Yb 3+ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce 3+ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H 2 O 2 to boost the CDT mediated by the Mn 2+ and Cu 2+ , which consequently realized a highly effective synergistic treatment for NSCLC. Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Biomimetic cell membrane camouflaged technology has drawn extensive attention as a feasible and efficient way to realize the biological functions of nanoparticles from the parent cells. As the burgeoning nanotherapeutic, the right-side-out orientation self-assembly and pathological dependent "on-demand" cargo release of cell membrane camouflaged nanocarriers remarkably limit further development for practical applications. In the present study, a spontaneously right-side-out-orientated coupling-driven ROS-sensitive nanotherapeutic has been constructed for target endothelial cells (ECs) repair through the synergistic effects of spontaneously right-side-out-orientated camouflaging. This condition results from the specific affinity between the intracellular domain of key transmembrane receptors band 3 on cell membrane inner leaflet and the corresponding P4.2 peptide-modified nanoparticles without the additional coextrusion. The "on-demand" cargo release results from the pathological ROS-cleavable prodrug. Particularly, the red blood cell camouflaged nanotherapeutics (RBC-LVTNPs) can enhance target drug delivery through low oscillatory shear stress (LSS) blood flow in the injured ECs lesion. Both in vitro and in vivo results collectively confirm that RBC-LVTNPs can restore the damaged ECs and function with the recovered vascular permeability and low inflammation microenvironment. The findings provide a powerful and universal approach for developing the biomimetic cell membrane camouflaged nanotechnology., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

In this study, a novel active chitosan (CH) packaging film that incorporates garlic leaf extract (GL) and stem cellulose nanocrystals (CNC) was prepared. The addition of CNC to the CH film increased its tensile strength, hydrophilicity, thermal stability, and water/oxygen barrier and decreased its water contact angle and weight-loss rate, while the addition of GL greatly enhanced its antioxidant and antibacterial activities. SEM and AFM analyses showed that the CNC agglomerates and deposits in the lower layer and the surface roughness of the film was the highest at 1.2 % concentration. The optimal composition of the film was determined to be 0.8 % CNC and 4 % GL by the fuzzy mathematics evaluation method. Then, black garlic was preserved with the optimized coating by electrostatic spraying and was found to slow water loss and migration, while its excellent antioxidant activities decreased the degree of browning during 90 d of storage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Photothermal therapy (PTT) is an effective treatment modality that is highly selective for tumor suppression and is a hopeful alternative to traditional cancer therapy. However, PTT-induced inflammatory responses may result in undesirable side effects including increased risks of tumor recurrence and metastasis. Here we developed multifunctional MnO nanoparticles as scavengers of proinflammatory molecules to alleviate the PTT-induced inflammatory response. The MnO nanoparticles improve the PTT therapy by (1) binding and scavenging proinflammatory molecules to inhibit the proinflammatory molecule-induced Toll-like receptors (TLR) activation and nuclear factor kappa B (NF-κB) signaling; (2) inhibiting activated macrophage-induced macrophage recruitment; and (3) inhibiting tumor cell migration and invasion. In vivo experimental results showed that further treatment with MnO nanoparticles after laser therapy not only inhibited the PTT-induced inflammatory response and primary tumor recurrence but also significantly reduced tumor metastasis due to the scavenging activity. These findings suggest that MnO nanoparticles hold the potential for mitigating the therapy-induced severe inflammatory response and inhibiting tumor recurrence and metastasis.

Oxidative stress is a key factor in the development of inflammatory diseases. Elimination of reactive oxygen species (ROS) in the inflamed colon has been confirmed as an effective strategy to alleviate inflammatory bowel disease (IBD). The conventional approaches will cause systemic absorption and potential side effects. To address these issues, we develop a nanomedicine (LS@PDA NPs) that is capable of delivering to target inflammatory lesions by electrostatic adsorption, subsequently effectively scavenging the excess ROS and alleviating inflammation to ameliorate ulcerative colitis (UC). In the DSS induced acute colitis mice model, LS@PDA NPs can significantly reduce the production of pro-inflammatory cytokines, alleviate oxidative stress, and promote the favorable recovery of the damaged colonic tissue. These results indicate that LS@PDA NPs are able to effectively alleviate intestinal inflammation and provide strong theoretical support for the treatment of other inflammatory diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Photodynamic therapy (PDT) is emerging as an efficient strategy to combat multidrug-resistant (MDR) cancer. However, the short half-life and limited diffusion of reactive oxygen species (ROS) undermine the therapeutic outcomes of this therapy. To address this issue, a tumor-targeting nanoplatform was developed to precisely deliver mitochondria- and endoplasmic reticulum (ER)-targeting PDT agents to desired sites for dual organelle-targeted PDT. The nanoplatform is constructed by functionalizing molybdenum disulfide (MoS 2 ) nanoflakes with glucose-modified hyperbranched polyglycerol (hPG), and then loading the organelle-targeting PDT agents. The resultant nanoplatform Cy7.5-TG@GPM is demonstrated to mediate both greatly enhanced internalization within MDR cells and precise subcellular localization of PDT agents, facilitating in situ near-infrared (NIR)-triggered ROS generation for augmented PDT and reversal of MDR, causing impressive tumor shrinkage in a HeLa multidrug-resistant tumor mouse model. As revealed by mechanistic studies of the synergistic mitochondria- and ER-targeted PDT, ROS-induced ER stress not only activates the cytosine-cytosine-adenosine-adenosine thymidine/enhancer-binding protein homologous protein (CHOP) pro-apoptotic signaling pathway, but also cooperates with ROS-induced mitochondrial dysfunction to trigger cytochrome C release from the mitochondria and induce subsequent cell death. Furthermore, the mitochondrial dysfunction reduces ATP production and thereby contributes to the reversal of MDR. This nanoplatform, with its NIR-responsive properties and ability to target tumors and subcellular organelles, offers a promising strategy for effective MDR 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 © 2022 Elsevier Ltd. All rights reserved.)

Chemotherapy, although effective against primary tumors, may promote metastasis by causing the release of proinflammatory factors from damaged cells. Here, polymeric nanoparticles that deliver chemotherapeutics and scavenge proinflammatory factors simultaneously to inhibit chemotherapy-induced breast cancer metastasis are developed. The cationic nanoparticles can adsorb cell-free nucleic acids (cfNAs) based on charge-charge interaction, which downregulates the expression of Toll-like receptors and then reduces the secretion of inflammatory cytokines. Through in vitro structural optimization, cationic polyamidoamine (PAMAM) dendrimers modified with drug-binding dodecyl groups and diethylethanolamine surface groups (PAMAM-G3-C12 5 -DEEA 20 ) exhibit the most desirable combination of nanoparticle size (≈140 nm), drug loading, cytotoxicity, cfNA binding, and anti-inflammatory activity. In the mouse models of breast cancer metastasis, paclitaxel-loaded nanoparticles reduce serum levels of cfNAs and inflammatory cytokines compared with paclitaxel treatment alone and inhibit both primary tumor growth and tumor metastasis. Additionally, no significant side effects are detected in the serum or major organs. These results provide a strategy to deliver chemotherapeutics to primary tumors while reducing the prometastatic effects of chemotherapy., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Plasmid DNA (pDNA) delivery has attracted extensive research interest due to its great potential in gene therapy. The design of efficient nano-vectors to promote cellular delivery and transfection of gene molecules is the key to success. Compared to conventional nanocarriers with spherical geometry, asymmetric nanoparticles have been well documented showing enhanced cellular uptake and drug delivery capability. However, the impact of asymmetric nanostructures on pDNA binding and following intracellular delivery performance has been less reported. Herein, asymmetric head-tail mesoporous silica nanoparticles (HTMSNs) with tailored tail lengths were synthesized and employed as nano-vectors for pDNA delivery. The nanostructures of HTMSNs were carefully characterized by electron tomography. The pDNA binding, cellular uptake and gene transfection capabilities of engineered asymmetric nanoparticles were compared with symmetric dendritic mesoporous silica nanoparticles (DMSNs). The results showed that the asymmetric morphology of nanoparticles promoted pDNA binding and cell internalization, where HTMSNs-66 with a specific tail length of 66 nm achieved the highest transfection efficiency. This study reveals the impact of asymmetric nanostructure on DNA interaction, and provides guidance in future designs of non-viral nano-vectors for efficient gene delivery.

This work demonstrates for the first time that a photochromic metal organic framework (pMOF) can be employed as a promising class of NIR-II photothermal material based on the photoinduced donor-acceptor intermolecular charge transfer process. After further surface-modification, such UV-activated pMOF-a nanoparticles allow the strong inhibition of 4T1 cancer cells under 1064 nm laser irradiation.

Nanomedicines represent new promising strategies for treating atherosclerosis (AS), because they enhance drug bioavailability and have lower side effects. Nevertheless, nanomedicines have several challenges with these advantages, including a limited circulation life, lack of precise targeting, and insufficient control of drug release. Accordingly, the development of drug delivery systems (DDSs) with abilities to enhance the payload delivery to the AS plaque lesion and to control drug release can boost the therapeutic efficacy and safety for AS treatment. Herein, we employed a one-step self-assembly approach for effectively encapsulating the anti-AS drug simvastatin (SIM) in zeolitic imidazolate framework-8 (ZIF-8) (SIM/ZIF-8), and then coated it with hyaluronic acid (HA) to fabricate the SIM/ZIF-8@HA nanoplatform. The resulting nanoplatform could efficiently accumulate in plaque regions through the specific recognition between HA and CD44. Meanwhile, the acid environment breaks down ZIF-8 to release SIM. The in vitro and in vivo experiments demonstrated that SIM/ZIF-8@HA could inhibit the proliferation of smooth muscle cells and have good biocompatibility. Moreover, SIM/ZIF-8@HA can effectively suppress the development of AS plaques without any considerable side effects in mice treatments. The findings revealed that SIM/ZIF-8@HA may be a promising nanomedicine for safe and efficient anti-AS applications.

Crystallization is a universal phenomenon underpinning many industrial and natural processes and is fundamental to chemistry and materials science. However, microscopic crystallization pathways of nanoparticle superlattices have been seldom studied mainly owing to the difficulty of real-time observation of individual self-assembling nanoparticles in solution. Here, using in situ electron microscopy, we directly image the full self-assembly pathway from dispersed nanoparticles into ordered superlattices in nonaqueous solution. We show that electron-beam irradiation controls nanoparticle mobility, and the solvent composition largely dictates interparticle interactions and assembly behaviors. We uncover a multistep crystallization pathway consisting of four distinct stages through multi-order-parameter analysis and visualize the formation, migration, and annihilation of multiple types of defects in nanoparticle superlattices. These findings open the door for achieving independent control over imaging conditions and nanoparticle assembly conditions and will enable further study of the microscopic kinetics of assembly and phase transition in nanocolloidal systems.

Polyhedron packings have fascinated humans for centuries and continue to inspire scientists of modern disciplines. Despite extensive computer simulations and a handful of experimental investigations, understanding of the phase behaviors of synthetic tetrahedra has remained fragmentary largely due to the lack of tetrahedral building blocks with tunable size and versatile surface chemistry. Here, we report the remarkable richness of and complexity in dimension-controlled assemblies of gold nanotetrahedra. By tailoring nanocrystal interactions from long-range repulsive to hard-particle-like or to systems with short-ranged directional attractions through control of surface ligands and assembly conditions, nearly a dozen of two-dimensional and three-dimensional superstructures including the cubic diamond and hexagonal diamond polymorphs are selectively assembled. We further demonstrate multiply twinned icosahedral supracrystals by drying aqueous gold nanotetrahedra on a hydrophobic substrate. This study expands the toolbox of the superstructure by design using tetrahedral building blocks and could spur future computational and experimental work on self-assembly and phase behavior of anisotropic colloidal particles with tunable interactions.

The conversion of CO 2 into value-added products is a compelling way of storing energy derived from intermittent renewable sources and can bring us closer to a closed-loop anthropogenic carbon cycle. The ability to synthesize nanocrystals of well-defined structure and composition has invigorated catalysis science with the promise of nanocrystals that selectively express the most favorable sites for efficient catalysis. The performance of nanocrystal catalysts for the CO 2 reduction reaction (CO 2 RR) is typically evaluated with nanocrystal ensembles, which returns an averaged system-level response of complex catalyst-modified electrodes with each nanocrystal likely contributing a different (unknown) amount. Measurements at single nanocrystals, taken in the context of statistical analysis of a population, and comparison to macroscale measurements are necessary to untangle the complexity of the ever-present heterogeneity in nanocrystal catalysts, achieve true structure-property correlation, and potentially identify nanocrystals with outlier performance. Here, we employ environment-controlled scanning electrochemical cell microscopy to isolate and investigate the electrocatalytic CO 2 RR response of individual facet-defined gold nanocrystals. Using correlative microscopy approaches, we conclusively demonstrate that {110}-terminated gold rhombohedra possess superior activity and selectivity for CO 2 RR compared with {111}-terminated octahedra and high-index {310}-terminated truncated ditetragonal prisms, especially at low overpotentials where electrode kinetics is anticipated to dominate the current response. The methodology framework described here could inform future studies of complex electrocatalytic processes through correlative single-entity and macroscale measurement techniques.

Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast-targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic-co-glycolic) acid cores, these nanoparticles, termed fibroblast membrane-camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor-β, interleukin (IL)-11, IL-13, and IL-17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof-of-concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad-spectrum therapy for fibrosis management., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Semiconducting zinc oxide nanoparticles (ZnO NPs) hold great potential as photocatalysts in wastewater treatment because of their favorable bandgap and cost-effectiveness. Unfortunately, ZnO NPs usually show rapid charge recombination that limits their photocatalytic efficacy significantly. Herein, we report a facile way of modifying ZnO NPs with zeolite imidazole framework-8 (ZIF8). A synergy between the two components may tackle the drawback of fast charge recombination for pristine ZnO NPs. Improved performance of photocatalytic degradation of methylene blue (MB) is confirmed by comparing with pristine ZnO and ZIF8 as the catalysts. The ZIF8 in the composite serves as a trap for photogenerated electrons, thus reducing the rate of charge recombination to enhance the photocatalysis rate. In addition, the hybridization process suppresses the aggregation of ZnO NPs, providing a large surface area and a greater number of active sites. Moreover, a small shift in the absorption band of ZnO@ZIF8 (10) NPs towards higher wavelength, also witnessed a little contribution towards enhanced photocatalytic properties. Mechanistic studies of the photocatalytic process of MB using ZnO@ZIF8 NPs catalyst reveal that hydroxyl radicals are the major reactive oxygen species. The facile hybridization of ZnO with ZIF8 provides a strategy for developing new photocatalysts with wide application potential., 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.)

Background: Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability., Materials and Methods: In the bionic system, gelatin was chosen as a carrier, and Fe 3 O 4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide., Results: In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm 2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in vivo. Moreover, compared with the bionic system group, the group treated with TNPs had significantly decreased liver and spleen signals in MR images and significantly enhanced liver and spleen signals in fluorescence images, indicating that the bionic system is less likely to be cleared by the reticuloendothelial system (RES) than TNPs, which may promote the accumulation of the bionic system at the site of the thrombus., Conclusion: These results suggest that the magnet-guided bionic system with LIFU responsiveness is an excellent candidate for targeting thrombi and holds promise as an innovative drug delivery system for thrombolytic therapy., Competing Interests: We declare that we have no conflicts of interest., (© 2022 Fang et al.)

An oxygen-irrelevant free radicals generation strategy has shown great potential in hypoxic tumor therapy. However, insufficient tumor accumulation, nonspecific intracellular localization, and the presence of highly reductive mitochondrial glutathione (GSH) dramatically hamper the free radicals therapeutic efficacy. Herein, a hierarchical targeting system was constructed by Fe-doped polydiaminopyridine nanoshuttles, indocyanine green (ICG), and an oxygen-irrelevant radicals generator (AIPH) to possess a negative charge. An acid-specific charge-reverse capability of the shuttles was achieved to enhance cell uptake in the tumor microenvironment (TME). In addition, the iron release occurs only in the acidic TME, which can be used as acidity enhancers to strengthen the charge-reverse process, thereby leading to more efficient tumor internalization and deep penetration. Moreover, such a nanosystem has significantly improved the delivery efficiency of nanoshuttles (16.06%) in the tumor tissues at 24 h postinjection, much higher than that of naked Fe-doped polydiaminopyridine (6.59%). More importantly, the nanoshuttles enable simultaneously mitochondria targeting and corresponding GSH depleting capability to show advantages in free radicals-based therapy after charge reversion, leading to a powerful tumor inhibition rate (>95%). The prescence of iron could allow for magnetic resonance imaging, while ICG allowed for photoacoustic imaging and fluorescence imaging to guide the therapeutic process. The remarkable features of the nanoshuttles may open a new avenue to explore an oxygen-irrelevant free radicals generating system for accurate cancer theranostics.

Poly (ethylene glycol) (PEG)-based nanomedicines are perplexed by the challenges of oxidation damage, immune responses after repeated injections, and limited excretion from the body. As an alternative to PEG, bioinspired zwitterions bearing an identical number of positive and negative ions, exhibit exceptional hydrophilicity, excellent biomimetic nature and chemical malleability, endowing zwitterionic nano-vectors with biocompatibility, non-fouling feature, extended blood circulation and multifunctionality. In this review, we innovatively classify zwitterionic nano-vectors into linear, hyperbranched, crosslinked, and hybrid nanoparticles according to different chemical architectures in rational design of zwitterionic nano-vectors for enhanced drug delivery with an emphasis on zwitterionic engineering innovations as alternatives of PEG-based nanomedicines. Through combination with other nanostrategies, the intelligent zwitterionic nano-vectors can orchestrate stealth and other biological functionalities together to improve the efficacy in the whole journey of drug delivery., (Copyright © 2022. Published by Elsevier B.V.)

Background: Comprehensive antitumor therapy through integrated multimodal means has drawn increasing attention owing to its high efficiency and metastasis suppression., Results: We describe a synergistic triple protocol combining photothermal and sonodynamic therapy (PTT and SDT), together with immune checkpoint blockade for the inhibition of breast cancer growth and metastases in the 4T1 mouse model. PTT and SDT are synergistically augmented by a novel multimodal imaging nanoprobe integrated with cancer cell membrane-biomimetic nanoparticles (CHINPs) loaded with superparamagnetic iron oxide (SPIO) and hematoporphyrin monomethyl ether (HMME). CHINPs exhibit excellent homologous tumor targeting, and are sequentially triggered by ultrasound and near infrared (NIR) light under the guidance of magnetic resonance, photoacoustic and photothermal imaging, leading to complete in situ tumor eradication and systemic anti-tumor immune activation. Further combination of this approach with immune checkpoint blockade therapy is shown to suppress tumor metastasis., Conclusion: This work provides proof-of-principle for triple therapy using multimodal imaging-guided PTT/SDT based on biomimetic nanoprobes in combination with immunotherapy to eliminate tumors., (© 2022. The Author(s).)

The precise delivery of multiple drugs to their distinct destinations plays a significant role in safe and efficient combination therapy; however, it is highly challenging to simultaneously realize the targets and overcome the intricate biological hindrances using an all-in-one nanosystem. Herein, a cascade-responsive hierarchical nanosystem containing checkpoint inhibitor anti-PD-L1 antibody (αPD-L1) and paclitaxel (PTX) is developed for spatially programed delivery of multiple drugs and simultaneously overcoming biological pathway barriers. The hierarchical nanoparticles (MPH-NP@A) are composed of pH-sensitive hyaluronic acid-acetal-PTX prodrugs (HA- ace -PTX(SH)) chaperoned by αPD-L1 and metalloproteinase-9 (MMP-9)-responsive outer shells, which could be fast cleaved to release αPD-L1 in the tumor microenvironment (TME). The released αPD-L1 sequentially synergizes with PTX released in the cytoplasm for boosted chemoimmunotherapy due to direct killing of PTX and intensified immune responses through immunogenic cell death (ICD) as well as suppression of immune escape by blocking the PD-1/PD-L1 axis. The in vitro and in vivo studies demonstrate that MPH-NP@A evokes distinct ICD, enhanced cytotoxic T lymphocytes infiltration, as well as significant tumor inhibition, thus providing a promising therapeutic nano-platform for safe and efficient combination therapy.

Stroke is the second leading cause of death globally and the most common cause of severe disability. Several barriers need to be addressed more effectively to treat stroke, including efficient delivery of therapeutic agents, rapid release at the infarct site, precise imaging of the infarct site, and drug distribution monitoring. The present study aimed to develop a bio-responsive theranostic nanoplatform with signal-amplifying capability to deliver rapamycin (RAPA) to ischemic brain tissues and visually monitor drug distribution. A pH-sensitive theranostic RAPA-loaded nanoparticle system was designed since ischemic tissues have a low-pH microenvironment compared with normal tissues. The nanoparticles demonstrated good stability and biocompatibility and could efficiently load rapamycin, followed by its rapid release in acidic environments, thereby improving therapeutic accuracy. The nano-drug-delivery system also exhibited acid-enhanced magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging signal properties, enabling accurate multimodal imaging with minimal background noise, thus improving drug tracing and diagnostic accuracy. Finally, in vivo experiments confirmed that the nanoparticles preferentially aggregated in the ischemic hemisphere and exerted a neuroprotective effect in rats with transient middle cerebral artery occlusion (tMCAO). These pH-sensitive multifunctional theranostic nanoparticles could serve as a potential nanoplatform for drug tracing as well as the treatment and even diagnosis of acute ischemic stroke. Moreover, they could be a universal solution to achieve accurate in vivo imaging and treatment of other diseases.

Currently, the combining photodynamic therapy (PDT) with photothermal therapy (PTT) modalities based on a single near infrared (NIR) laser irradiation and highly selective internalization still remain a challenge. Herein, a hierarchical dual-responsive cleavable nanosystem for synergetic NIR triggered PDT/PTT is reported. The engineered nanoplatform (Au NRs/Cur/UCNPs@PBE) is designed by loading curcumin (Cur, photosensitizer) on gold nanarods (Au NRs) to build PDT/PTT therapy system, which was encapsulated outside with upconversion nanoparticles (UCNPs) and then modified with phenylboronic double ester (PBE). The pH and ROS-responsive feature made Au NRs/Cur/UCNPs@PBE provide a fundamental structural evolution and improve the specificity and intracellular accumulation to tumors. Au NRs/Cur/UCNPs@PBE exhibited significant PDT and PTT efficiency against two type melanoma cells due to upconversion nanoparticles and Au NRs induced by an 808 nm laser. Notably, the platform can mainly activate apoptosis and partial ferroptosis to achieve the synergistic PDT/PTT, furthermore, the integrated PDT with PTT using Au NRs/Cur/UCNPs@PBE showcased a great antitumor efficacy in vivo superior to the other alone treatment. Our findings highlight that this intelligent nanoagents for synergistic phototherapy facilitate enhanced fighting melanoma and provide a promising strategy for melanoma theranostics., (Copyright © 2021. Published by Elsevier B.V.)

Ferroptosis-based nanomedicine has drawn increasing attention in antitumor therapy because of the advantages of this unconventional mode of apoptosis, but the difficulties of delivery to the tumor site and surface-to-core penetration after arrival seriously hinder further clinical transformation and application. Herein, we propose an unprecedented strategy of injecting magnetic nanodroplets (MNDs) to solve these two longstanding problems. MNDs are nanocarriers that can carry multifunctional drugs and imaging materials. MNDs can effectively accumulate in the tumor site by active tumor targeting (multifunctional drugs) and passive tumor targeting (enhanced permeability and retention effect), allowing diffusion of the MNDs from the surface to the core through mild-temperature magnetic fluid hyperthermia (MHT) under multimodal imaging guidance. Finally, the ferroptosis pathway is activated deep within the tumor site through the drug release. This approach was inspired by the ability of mild-temperature MHT to allow MNDs to quickly pass through the blood vessel-tumor barrier and deeply penetrate the tumor tissue from the surface to the core to amplify the antitumor efficacy of ferroptosis. This strategy is termed as "thermoferroptosis sensitization". Importantly, this behavior can be performed under the guidance of multimodal imaging, making the design of MNDs for cancer therapy safer and more reasonable., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Micro- and nano- polystyrene particles have been widely detected in environment, posing potential threats to human health. This study was designed to evaluate the neurodevelopmental toxicity of polystyrene nanoparticles (NPs) in Caenorhabditis elegans (C. elegans), to screen crucial genes and investigate the underlying mechanism. In wild-type C. elegans, polystyrene NPs (diameter 50 nm) could concentration-dependently induce significant inhibition in body length, survival rate, head thrashes, and body bending, accompanying with increase of reactive oxygen species (ROS) production, lipofuscin accumulation, and apoptosis and decrease of dopamine (DA) contents. Moreover, pink-1 mutant was demonstrated to alleviate the locomotion disorders and oxidative damage induced by polystyrene NPs, indicating involvement of pink-1 in the polystyrene NPs-induced neurotoxicity. RNA sequencing results revealed 89 up-regulated and 56 down-regulated differently expressed genes (DEGs) response to polystyrene NPs (100 μg/L) exposure. Gene Ontology (GO) enrichment analysis revealed that predominant enriched DEGs were correlated with biological function of cuticle development and molting cycle. Furthermore, mutant strains test showed that the neurodevelopmental toxicity and oxidative stress responses induced by 50 nm polystyrene NPs were regulated by dpy-5 and rol-6. In general, polystyrene NPs induced obvious neurodevelopmental toxicity in C. elegans through oxidative damage and dopamine reduction. Crucial genes dpy-5 and rol-6 might participate in polystyrene NPs-induced neurodevelopmental toxicity through regulation on synthesis and deposition of cuticle collagen., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Controlling the size and morphology of metal-organic frameworks (MOF) has received increasing research interest but remains a great challenge. In this work, we demonstrate a trace-water-induced competitive coordination procedure to controllably synthesize porphyrinic MOFs including needle-shaped nanomaterials, hollow nanotubes, and nanocubes, using 5,10,15,20-tetrakis(4-carboxyphenyl) porphyrin as organic linkers and Zr 4+ as inorganic building blocks. These three MOFs exhibited shape-dependent singlet oxygen ( 1 O 2 ) production under 655 nm laser irradiation. The designed nanocubes were functionalized by coating a MnO 2 shell, which can effectively generate 1 O 2 in the tumor microenvironment (TME) to improve photodynamic therapy (PDT). Moreover, they reacted with GSH, and the resulted Mn 2+ ions generated hydroxyl radicals (·OH) for chemodynamic therapy (CDT). Therefore, the designed MOFs@MnO 2 nanoparticles were responsive to the hypoxic TME to improve the efficiency of PDT and incorporate CDT for tumor ablation.

Purpose: Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women of reproductive age and leads to metabolic disorders and infertility. The present study was conducted to investigate the therapeutic effects of curcumin (Cur) encapsulated arginine (Arg) and N-acetyl histidine (NAcHis) modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles (NPs)., Methods: In this study, amphiphilic chitosan (CS) conjugate was developed by modification with hydrophilic arginine (Arg) and hydrophobic N-acetyl histidine (NAcHis) group (Arg-CS-NAcHis). The synthesized conjugate was well characterized by FTIR and NMR studies. Self-assembled nanoparticles based on the synthesized conjugate were developed by simple sonication method and characterized for the physicochemical properties of zeta potential, particle size and drug encapsulation. Next, in vitro drug release, cytotoxicity, and cellular uptake studies of the NPs were evaluated. Finally, the developed nanoparticles were examined for their therapeutic potential against estradiol valerate (EV) induced PCOS rats by evaluating hormone level changes and ovarian morphology., Results: The results showed that zeta potential of the nanoparticles was 39.8±2.52 mV and the average size was 200 nm. The in vitro drug release profile showed sustained release pattern. Cytotoxicity and cellular uptake studies also showed preferential effectiveness than free curcumin. Both the biochemical and histopathological studies showed positive effects in reverting the symptoms of PCOS rats to normalcy., Conclusion: Curcumin encapsulated arginine and N-acetyl histidine modified chitosan (Arg-CS-NAcHis/Cur) nanoparticles have been successfully developed. The present study suggested that treatment of the nanoparticles might reverse many of the PCOS symptoms. Therefore, these nanoparticles might be used as promising new candidate for delivery of curcumin to treat PCOS., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Raja et al.)

Sonodynamic therapy (SDT) is a highly promising approach for cancer therapy, but its efficacy is severely hampered by the low specificity of sonosensitizers and the unfavorable characteristics of the tumor microenvironment (TME), such as hypoxia and glutathione (GSH) overexpression. To solve these problems, in this work, we encapsulated IR780 and MnO 2 in PLGA and linked Angiopep-2 (Ang) to synthesize a multifunctional nanozyme (Ang-IR780-MnO 2 -PLGA, AIMP) to enhance SDT. With Ang functionalization to facilitate blood-brain barrier (BBB) penetration and glioma targeting, and through the function of IR780, these nanoparticles (NPs) showed improved targeting of cancer cells, especially mitochondria, and spread deep into tumor centers. Upon low-intensity focused ultrasound (LIFU) irradiation, reactive oxygen species (ROS) were produced and induced tumor cell apoptosis. Combined with the specific mitochondria-targeting ability of IR780, the sonodynamic effects were amplified because mitochondria are sensitive to ROS. In addition, MnO 2 exhibited enzyme-like activity, reacting with the high levels of hydrogen protons (H + ), H 2 O 2 and GSH in the TME to continuously produce oxygen and consume GSH, which further enhanced the effect of SDT. Moreover, Mn 2+ can be released in response to TME stimulation and used as a magnetic resonance (MR) contrast agent. In addition, IR780 has photoacoustic (PA)/fluorescence (FL) imaging capabilities. Our results demonstrated that AIMP NPs subjected to LIFU triggering maximally enhanced the therapeutic effect of SDT by multiple mechanisms, including multiple targeting, deep penetration, oxygen supply in situ and GSH depletion, thereby significantly inhibiting tumor growth and distal metastasis without systemic toxicity. In summary, this multifunctional nanozyme provides a promising strategy for cancer diagnosis and treatment under the intelligent guidance of multimodal imaging (PA/FL/MR) and may be a safe clinical translational method.