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Background: Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed., Methods: In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR., Results: We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression., Conclusion: Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction., Competing Interests: 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., (© 2024 Li et al.)

Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS-targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose-dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP-loaded non-bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes-associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies., (© 2023 Wiley‐VCH GmbH.)

The study proposed improving the arsenic encapsulation efficiency (EE) in liposomes and make it pH responsive. Liposomes were prepared using the ethanol injection method (EIM), thin film dispersion method (TFM) and CAGM with sodium arsenite (NaAsO 2 ). The orthogonal experimental was used to optimize the preparation conditions of the CAGM. The arsenic-carrying liposomes were characterized by polydispersity index (PDI), transmission electron microscopy (TEM), in vitro release experiments and inductively coupled plasma emission spectrum (ICP). The toxicity was investigated by rat glioma cells (C6) and human brain micro vascular endothelial cells (HBMEC). The results indicated that the CAGM can effectively improve the EE of NaAsO2 and has a pH response compared with EIM and TFM. The size of nanoparticles prepared by CAGM was 118.8 ±56.67 nm, the arsenic EE was 54.3 ±9.82%, the drug loading rate was 7.13 ±0.72% (P <0.01), pH sensitivity was shown at pH 5.5. The optimal parameters of the CAGM were 3 mg NaAsO2, 5:1 egg phosphatidylcholine (EPC) to cholesterol (CHOL) and 240 mmol/L calcium acetate (CaAC2). The results showed that the CAGM has good biocompatibility and is one of the effective ways to improve the NaAsO2 encapsulation rate and pH response in liposome nanoparticles.

Histone deacetylases (HDACs) are a class of epigenetic enzymes that are closely related to tumorigenesis and suppress the expression of tumor suppressor genes. Whereas the HDACs inhibitors can release DNA into the cytoplasm and trigger innate immunity. However, the high density of chromatin limits DNA damage and release. In this study, suitable nanosized CycNHOH NPs (150 nm) and CypNHOH NPs (85 nm) efficiently accumulate at the tumor site due to the enhanced permeability and retention (EPR) effect. In addition, robust single-linear oxygen generation and good photothermal conversion efficiency under NIR laser irradiation accelerated the DNA damage process. By effectively initiating immune cell death, CypNHOH NPs activated both innate and adaptive immunity by maturing dendritic cells, infiltrating tumors with natural killer cells, and activating cytotoxic T lymphocytes, which offer a fresh perspective for the development of photo-immunotherapy., (© 2023 Wiley‐VCH GmbH.)

Accumulating evidence supports the notion that microglia play versatile roles in different chronic pain conditions. However, therapeutic strategies of chronic pain by targeting microglia remain largely overlooked. This study seeks to develop a miRNA-loaded nano-delivery system by targeting microglia, which could provide a decent and long-lasting analgesia for chronic pain. Surface aminated mesoporous silica nanoparticles were adopted to load miR-26a-5p, a potent analgesic miRNA, by electrostatic adsorption, which can avoid miR-26a-5p is rapidly released and degraded. Then, targeting peptide MG1 was modified on the surface of aminated mesoporous silica particles for microglia targeting. In peripheral nerve injury induced neuropathic pain model, a satisfactory anti-allodynia effect with about 6 weeks pain-relief duration were achieved through targeting microglia strategy, which decreased microglia activation and inflammation by Wnt5a, a non-canonical Wnt pathway. In inflammatory pain and chemotherapy induced peripheral neuropathic pain, microglia targeting strategy also exhibited more efficient analgesia and longer pain-relief duration than others. Overall, we developed a microglia-targeting nano-delivery system, which facilitates precisely miR-26a-5p delivery to enhance analgesic effect and duration for several chronic pain conditions., (© 2024. The Author(s).)

Skin graft rejection is a significant challenge in skin allografts for skin defects, particularly in extensive burn injury patients when autografts are insufficient. Enhancing the survival duration of allogeneic skin grafts can improve the success rate of subsequent autologous skin grafting, thereby promoting the therapeutic efficacy for wound healing. Rapamycin (Rapa), a potent immunosuppressant with favorable efficacy in organ transplantation, is limited by its systemic administration-associated toxicity and side effects. Therefore, addressing the short survival time of allogeneic skin grafts and minimizing the toxicity related to systemic application of immunosuppressive agents is an urgent requirement. Here, we present a topical formulation based on bioadhesive poly (lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs) with surface-modified encapsulation of Rapamycin (Rapa/BNPs), applied for local immunosuppression in a murine model of allogeneic skin grafts. Our Rapa/BNPs significantly prolong nanoparticle retention, reduce infiltration of T lymphocytes and macrophages, decrease the level of pro-inflammatory cytokines and ultimately extend skin allograft survival with little systemic toxicity compared to free Rapa or Rapamycin-loaded non-bioadhesive nanoparticles (Rapa/NNPs) administration. In conclusion, Rapa/BNPs effectively deliver local immunosuppression and demonstrate potential for enhancing skin allograft survival while minimizing localized inflammation, thus potentially increasing patient survival rates for various types of skin defects., 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.)

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)-based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt-based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin-encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi-omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: Multiple stages including hemostasis, inflammation, proliferation, and remodeling were involved in the wound healing process. The increase in nanomaterials in recent years has extended the scope of tools for wound healing; however, it is still difficult to achieve the four multistage procedures simultaneously., Materials and Methods: In this study, graphene-spiky silica heterostructured nanoparticles (GS) were synthesized for the procedural acceleration of the multistage in wound healing process. The nanobridge effect of GS was analyzed through the adhesion of two skins, the antibacterial effect was assessed in Gram-negative Escherichia coli ( E. coli ) and Gram-positive Staphylococcus aureus ( S. aureus ) bacteria, cell proliferation and migration were investigated in mouse embryonic fibroblast (NIH-3T3) cells, and the in vivo wound healing effect was examined in female BALB/c mice with a cutting wound and E. coli or S. aureus bacteria infection on the back., Results: First, GS has a strong nanobridge effect on the rapid closure of wounds because the spiky architecture on the surface of GS facilitates the adhesion of skins, promoting the hemostasis stage. Second, graphene exhibits antimicrobial activities both in chemical and physical interactions, especially under simulated sunlight irradiation. Third, graphene plays an important role in scaffolding function, together with the spiky topographical architecture of GS, accelerating the proliferation and maturation stages., Conclusion: By periodically promoting every stage of wound healing, GS combined with simulated sunlight irradiation could significantly accelerate wound healing. With a simple composition and compact structure but multiple functions, this strategy will be the guideline for the development of ideal wound-healing nanomaterials., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Li et al.)

Purpose: The purpose of this study was to improve the immune compatibility and targeting abilities of IL10 nanoparticles coated with platelet membrane (IL10-PNPs) by glycosylation engineering in order to effectively reduce restenosis after vascular injury., Materials and Methods: In this study, we removed sialic acids and added α (1,2)-fucose and α (1,3)-fucose to platelet membrane glycoprotein, thus engineering the glycosylation of IL10-PNPs (IL10-GE-PNPs). In vitro and in vivo experiments were conducted to evaluate the targeting and regulatory effects of IL10-GE-PNPs on macrophage polarization, as well as the influence of IL10-GE-PNPs on the phenotypic transformation, proliferation, and migration of smooth muscle cells, and its potential in promoting the repair function of endothelial cells within an inflammatory environment. In order to assess the distribution of IL10-GE-PNP in different organs, in vivo imaging experiments were conducted., Results: IL10-GE-PNPs were successfully constructed and demonstrated to effectively target and regulate macrophage polarization in both in vitro and in vivo settings. This regulation resulted in reduced proliferation and migration of smooth muscle cells and promoted the repair of endothelial cells in an inflammatory environment. Consequently, restenosis after vascular injury was reduced. Furthermore, the deposition of IL10-GE-PNPs in the liver and spleen was significantly reduced compared to IL10-PNPs., Conclusion: IL10-GE-PNPs emerged as a promising candidate for targeting vascular injury and exhibited potential as an innovative drug delivery system for suppressing vascular restenosis. The engineered glycosylation of IL10-PNPs improved their immune compatibility and targeting abilities, making them an excellent therapeutic option., Competing Interests: 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., (© 2023 Li et al.)

Traditional antibacterial procedures are getting inefficient due to the emergence of antimicrobial resistance, which makes alternative treatments in urgent demand. However, the selectivity toward infectious bacteria is still challenging. Herein, by taking advantage of the self-directed capture of infectious bacteria by macrophages, we developed a strategy to realize precise in vivo antibacterial photodynamic therapy (APDT) through adoptive photosensitizer-loaded macrophage transfer. TTD with strong reactive oxygen species (ROS) production and bright fluorescence was first synthesized and was subsequently formulated into TTD nanoparticles for lysosome targeting. TTD-loaded macrophages (TLMs) were constructed by direct incubation of TTD nanoparticles with macrophages, in which the TTD was localized in the lysosomes to meet the captured bacteria in the phagolysosomes. The TLMs could precisely capture and eradicate bacteria while being activated toward the proinflammatory and antibacterial M1 phenotype upon light illumination. More importantly, after subcutaneous injection, TLMs could effectively inhibit bacteria in the infected tissue through APDT, leading to good tissue recovery from severe bacterial infection. Overall, the engineered cell-based therapeutic approach shows great potential in the treatment of severe bacterial infectious diseases.

Asymmetrical heptamethine cyanine with near-infrared (NIR) absorption is used for photothermal therapy (PTT) of cancer. Aiming to overcome the drawbacks caused by the high temperature of PTT, the development of asymmetrical heptamethine cyanine with photothermal and photodynamic properties is still an attractive strategy. Different from the traditional method of the heavy atom effect, in this work, the carboxyl or sulfonic groups are introduced into the indole ring or branch chain of asymmetrical heptamethine cyanine to afford a series of new phototherapy agents. After being encapsulated by DSPE-PEG 2000 , BSS-Et NPs exhibit robust photostability, efficient reactive oxygen species generation (49%), and excellent photothermal conversion efficiency of about 37.6% under 808 nm laser irradiation. BSS-Et NPs possess passive tumor-targeting properties in vivo to not only visualize the tumor by NIR fluorescence imaging but also eliminate the tumor without any recurrence by photodynamic therapy and PTT synergistic therapy under laser irradiation. In addition, benefitting from the characteristics of organic small molecules, they can be metabolized quickly through the liver without inducing toxicity in the whole body. In general, this study provides a new direction for the development of multifunctional phototherapy agents for cancer treatment., (© 2023 Wiley-VCH GmbH.)

Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.

Designing metal-metal oxide heteronanostructures with synergistic and superior activities (unattainable in the case of a single entity) is of great interest for a wide range of technological applications. Traditional synthetic strategies typically require reducing agents, stabilizing ligands, or high temperature reductive treatment to produce oxide-supported metals. Herein, a facile noble metal deposition strategy is developed to produce silver, gold, and platinum nanocrystals on the surface of hollow mesoporous cerium oxide nanospheres without any pretreatment. Unlike the galvanic replacement reaction, the developed protocol employs the innate reductive potential of CeO 2 to produce a high density of ultrafine noble metal nanocrystals homogeneously immobilized onto the surface of CeO 2 nanospheres. The multienzyme-like activities (i.e., superoxide dismutase-like and catalase-like) of CeO 2 @metal nanostructures, originating from CeO 2 and metal nanoparticles, were effectively utilized for anti-inflammatory therapies in two in vivo models. This oxygen vacancy-mediated reduction strategy can be generalized to produce diverse metal-metal oxide nanostructures for a wide range of applications.

Ultrasound has a recognized ability to modulate the structure and function of proteins. Discovering the influential mechanism of ultrasound on the intramolecular interactions of egg-white protein isolate-curcumin (EPI-Cur) nanoparticles and their intermolecular interaction during freeze drying and redispersion is meaningful. In this study, under the extension of pre-sonication time, the protein solubility, surface hydrophobicity, and curcumin encapsulation rate showed an increasing trend, reaching the highest value at 12 min of treatment. However, the values decreased under the followed extension of ultrasound time. After freeze drying and redispersion were applied, the EPI-Cur sample under 12 min of ultrasound treatment exhibited minimal aggregation degree and loss of curcumin. The retention and loading rates of curcumin in the lyophilized powder reached 96 % and 33.60 mg/g EPI, respectively. However, under excessive ultrasound of >12 min, scanning electron microscopy showed distinct blocky aggregates. Overexposure of the hydrophobic region of the protein triggered protein-mediated hydrophobic aggregation after freeze drying. X-ray diffraction patterns showed the highest crystallinity, indicating that the free curcumin-mediated hydrophobic aggregation during freeze drying was enhanced by the concentration effect and intensified the formation of larger aggregates. This work has practical significance for developing the delivery of hydrophobic active substances. It provides theoretical value for the dynamic dispersity change in protein-hydrophobic active substances during freeze drying and redissolving., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

NIR-II fluorescence imaging (NIR-II FI) and photothermal therapy (PTT) have received broad attentions in precise tumor diagnosis and effective treatment attributed to high-resolution and deep tissue imaging, negligible invasivity, and high-efficiency treatment. Although many fluorescent molecules have been designed and conducted for NIR-II FI and PTT, it is still an enormous challenge for researchers to pioneer some rational design guidelines to improve fluorescence brightness. Organic D-A-type molecules, including small molecules and conjugated polymers, can be designed and developed to improve fluorescence brightness due to their tunable and easy functionalized chemical structures, allowing molecules tailored photophysical properties. In this review, some approaches to the development and design strategies of D-A type small molecules and conjugated polymers for the enhancement of fluorescence brightness are systemically introduced. Meanwhile, some applications of PTT and PTT-based combination therapy (such as PDT, chemotherapy, or gas therapy) assisted by NIR-II FI-based single or multiimaging technologies are classified and represented in detail as well. Finally, the current issues and challenges of NIR-II organic molecules in NIR-II FI-navigated PTT are summarized and discussed, which gives some guidelines for the future development direction of NIR-II organic molecules for NIR-II FI-navigated PTT., (© 2022 Wiley-VCH GmbH.)

Intracellular transport plays an important role in maintaining the physiological functions of cells. Here, we describe a protocol for 3D single-particle tracking within living cells. We detail the use of a two-focal imaging system and the analytical steps for quantifying 3D transport dynamics. This protocol can be used to characterize the intracellular diffusion and trafficking of macromolecules, nanoparticles, and endocytic vesicles in adherent cells. For complete details on the use and execution of this protocol, please refer to Jiang et al. (2022)., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Nanoparticles based on bovine serum albumin (BSA), which shares 76% homology with human serum albumin (HSA), have emerged as a promising candidate for the efficient delivery of anticancer drugs. Thermal-driven self-assembly is a novel organic solvent-free approach to produce albumin nanoparticles. In our previous study, some features of this nanoparticle such as drug loading efficiency, drug encapsulation efficiency and drug release kinetics have been evaluated. However, the formation mechanism that determines the above nanoparticle properties remains unclear. Here, we investigated the formation kinetics and mechanism using spectroscopic methods including fluorescence spectroscopy, circular dichroism (CD) and differential scanning calorimetry (DSC). We also applied chemical analysis methods that measured the content changes of albumin active groups and vanillin. To verify the covalent networks in the nanoparticles, trypsin and glutathione (GSH) were used separately to cleave the peptide bonds and disulfide bridges, and dynamic light scattering (DLS) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) were used to analyze the degraded samples. BSA nanoparticles started to form at 10 min and were completely formed at 120 min. With the digestion of trypsin, more than 50% of the nanoparticles were degraded within 60 min. CD spectra showed that α-helical structure of BSA decreased from 42.3% to 39.8% and 37.7% after heating for 10 and 60 min, respectively. In the DSC thermogram, the melting peak of BSA nanoparticles was 229.14℃, which is about 12℃ higher than the physical mixture of BSA and vanillin, indicating that chemical reactions occurred during the nanoparticle formation and formed a new more stable substance. Moreover, the results of active group assay, GSH degradation and SDS-PAGE experiments also proved that disulfide bonds and peptide bonds were formed between BSA molecules, whereas Schiff bases were formed between BSA and vanillin molecules. Formation kinetics and degradation behavior are important properties to characterize albumin nanoparticles and should be paid attention to. Not only that, this study also provides an effective way to study the formation mechanism of protein-based nanodrug delivery systems., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

A self-preservation Pt(IV) nanoplatform, amorphous ferric oxide-coating selenium core-shell nanoparticles (iAIO@NSe-Pt), was developed for H 2 O 2 depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis. Upon entry into the blood, the ferric oxide shell effectively blocked the contact Pt(IV) prodrug with reduced molecules, then avoided the inactivation of the Pt(IV) prodrug and increased its accumulation in the tumor. After entering cancer cells, iAIO@NSe-Pt caused a series of cascade reactions: (1) AIO on the surface of iAIO@NSe-Pt quickly dissolved, released an abundance of Fe(II) because of the weakly acidic tumor microenvironment, and then catalyzed cellular H 2 O 2 into highly toxic ˙OH, resulting in cellular H 2 O 2 deficiency and cell ferroptosis. (2) The platinum(IV) prodrugs were exposed and quickly reduced to highly toxic Pt(II) by depleting GSH. This process inactivated GPX4, promoted ROS accumulation, and further accelerated ferroptosis. In addition, the generated Pt(II) quickly inhibited DNA replication, achieving effective apoptotic cell death. Meanwhile, Pt(II) inactivated SOD1, which blocked the synthesis of cellular H 2 O 2 and accelerated ROS (superoxide anion radical) accumulation. (3) The deficiency of cellular H 2 O 2 significantly inhibited the expression of vascular endothelial growth factor-A (VEGF-A), blocking tumor angiogenesis and then improving the anticancer effect. (4) After such a cascade reaction, the exposed NSe successively disrupted mitochondrial respiration and inhibited cancer angiogenesis, further inducing cancer cell death. Collectively, our functional and mechanical investigation suggested that iAIO@NSe-Pt exhibits excellent tumor targeting, biocompatibility and anti-tumor efficiency in vitro and in vivo , and provides a novel example of a self-preservation Pt(IV) nanoplatform for H 2 O 2 depletion-mediated tumor anti-angiogenesis, apoptosis, and ferroptosis, showing great promise for future clinical use.

Leukemia is a non-solid cancer which features the malignant proliferation of leukocytes. Excessive leukocytes of lesions in peripheral blood will infiltrate organs, resulting in intumescence and weakening treatment efficiency. In this study, we proposed a novel approach for targeted clearance of the leukocytes in the peripheral blood ex vivo, which employed magnetic nanochains to selectively destroy the leukocytes of the lesions. The nanochains were doxorubicin-loaded nanochains of Fe 3 O 4 nanoparticles which were fabricated by the solvent exchange method combined with magnetic field-directed self-assembly. Firstly, the nanochains were added into the peripheral blood during extracorporeal circulation and subjected to a rotational magnetic field for actuation. The leukocytes of the lesion were then conjugated by the nanochains via folic acid (FA) targeting. Finally, the rotational magnetic field actuated the nanochains to release the drugs and effectively damage the cytomembrane of the leukocytes. This strategy was conceptually shown in vitro (K562 cell line) and the method's safety was evaluated in a rat model. The preliminary results demonstrate that the nanochains are biocompatible and suitable as drug carriers, showing direct lethal action to the leukemic cells combined with a rotational magnetic field. More importantly to note is that the nanochains can be effectively kept from entry into the body. We believe this extracorporeal circulation-based strategy by activating nanochains magnetically could serve as a potential method for leukemia treatment in the future.

We explored the catalytic activity and magnetic resonance imaging (MRI) capacity of Cu-doped ultrasmall iron oxides with different doping ratios. Then, we screened a highly efficient ultrasmall active catalyst (UAC). Subsequently, a biodegradable magnetic nanoliposome was developed for multimodal cancer theranostics through pH-sensitive liposome coating of these UACs. Upon entering the body, the magnetic nanoliposomes significantly prolonged the metabolic time of UACs and promoted their accumulation in tumors. Then, the strong photothermal (PT) effect of the magnetic nanoliposome quickly ablated the tumor, showing promising PT therapy. Upon entering tumor cells, the magnetic nanoliposome rapidly degraded into many UACs and released chemotherapeutic drugs, contributing to chemotherapy. In addition, UACs not only catalyzed Fenton-type reaction to produce excessive reactive oxygen species (ROS) but also inhibited the synthesis of endogenous GSH by inactivating glutamyl cysteine ligase, contributing to cancer ferroptosis. Furthermore, the assembly-dissociation process of UACs showed the function of magnetic relaxation switches, significantly enhancing tumor MRI signal change, achieving a more accurate diagnosis of the tumor. Therefore, this magnetic nanoliposome splits into many UACs upon drug release and regulates the tumor microenvironment to overproduce ROS for enhanced synergistic tumor theranostics, which provides a strategy for developing next-generation magnetic catalysts with biodegradability and multimodal antitumor theranostics.

Self-assembly processes, while promising for enabling the fabrication of complexly organized nanomaterials from nanoparticles, are often limited in creating structures with multiscale order. These limitations are due to difficulties in practically realizing the assembly processes required to achieve such complex organizations. For a long time, a hierarchical assembly attracted interest as a potentially powerful approach. However, due to the experimental limitations, intermediate-level structures are often heterogeneous in composition and structure, which significantly impacts the formation of large-scale organizations. Here, we introduce a two-stage assembly strategy: DNA origami frames scaffold a coordination of nanoparticles into designed 3D nanoclusters, and then these clusters are assembled into ordered lattices whose types are determined by the clusters' valence. Through modulating the nanocluster architectures and intercluster bindings, we demonstrate the successful formation of complexly organized nanoparticle crystals. The presented two-stage assembly method provides a powerful fabrication strategy for creating nanoparticle superlattices with prescribed unit cells.

Zeolitic imidazolate framework-8 (ZIF-8) is a type of Metal-organic frameworks (MOFs), which shows promising application in the field of bacterial infection, owing to its excellent biocompatibility. Here, we report the encapsulation of silver nanoparticles (Ag NPs) in ZIF-8, accompanied with embedding of physcion (Phy) to obtain Ag-Phy@ZIF-8 with efficient and intelligent synergistic antimicrobial capabilities. Due to the micro-acidic environment around the bacteria, the release of silver and Phy shows a controlled released. Further, the Ag-Phy@ZIF-8 is modified by hyaluronate (HA), denoted as Ag-Phy@ZIF-8@HA, which has a strong inhibitory effect on the growth of both E. coli (99.1%) and S. aureus (99.5%), with no impacting on cell growth, showing good biocompatibility. Thus, these pH-responsive biocomposites have the potential application on smart wound excipients for bacterial infections., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The study aimed to analyze the value and significance of magnetic resonance imaging (MRI) using biocompatible Au-Fe3O4 nanomaterials in the diagnosis of liver tumors. In this study, 124 patients with liver tumors were selected to perform MRI scanning based on Au-Fe3O4 nanoparticles. The coincidence rate between MRI scanning results and pathological examination results, the detection rate of tumor focus between MRI scanning results and CT detection results were analyzed, to evaluate the diagnostic performance of MRI scanning based on Au-Fe3O4 nanoparticles. The results showed that in the detection of primary tumors, secondary tumors, and focal nodular hyperplasia, the coincidence rate between MRI scanning results and pathological examination results was high, and Kappa values were all greater than 0.8. Compared with the results of CT, the detection rate of tumor lesions smaller than 1 cm by MRI was significantly higher (P<0.05), but there was no significant difference between the two diagnostic methods for tumor lesions larger than 1 cm (P>0.05). Additionally, the accuracy, specificity, and sensitivity of MRI in diagnosing liver tumors were 86.81, 84.29, and 77.27, respectively. Clinically, MRI scanning based on Au-Fe3O4nanoparticles can provide a practical and effective reference for the differential diagnosis of liver tumors.

Developing high-performance catalysts for water splitting via renewable electricity is of great significance for the clean production of hydrogen. This work reports rational design and controllable fabrication of metal oxide hybrid catalyst CoNiFe 2 O 5 ·2CuO with unique biphasic microstructures for electrochemical water splitting. Benefited from the presence of CuO nanoparticles as the second phase, more defects and active sites were formed around the interfaces of CoNiFe 2 O 5 and CuO, which led to excellent performances for electrocatalytic water splitting. In particular, the catalyst exhibited outstanding activity for hydrogen evolution reaction with a small overpotential of 30 mV to reach a current density of 10 mA cm -2 and showed a higher turnover frequency (0.3 s -1 ) than commercial catalyst Pt/C (0.1 s -1 ) under an overpotential of 50 mV. Moreover, it also displayed good activity for oxygen evolution reaction with an overpotential of 264 mV at 10 mA cm -2 . Using CoNiFe 2 O 5 ·2CuO as the catalyst for electrode pair to construct a cell, a very low cell voltage of 1.53 V is enough to achieve overall water splitting at 10 mA cm -2 in 1 M KOH electrolyte, and the cell could maintain the stable performance at 10 mA cm -2 within 100 h. The as-prepared metal oxide hybrids with biphasic microstructures may have promising application potentials in water splitting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Herein, we developed a novel transferrin protein corona (Tpc)-modified CuGd nanoplatform (Tpc-CuGd) for tumor-targeting photothermal (PT) and chemodynamic synergistic therapy. In addition, Tpc-CuGd had an ultrahigh PT conversion efficiency (∼55.6%) and excellent PT stability. By the calculation, the Fenton-catalytic activity of Tpc-CuGd was approximately 13.6 times that of classical ultrasmall iron oxide, endowing strong chemodynamic therapy ability in the tumor. Upon internalization of Tpc-CuGd nanoparticles (NPs), an abundance of Cu(II) was released from Tpc-CuGd and then was quickly reduced to high Fenton-catalytic activity of Cu(I) by elemental copper and cellular GSH. Next, the generated Cu(I) quickly catalyzed H 2 O 2 into highly toxic • OH, causing mitochondria damage and inducing cancer cell death. In addition, the systemic delivery of Tpc-CuGd significantly inhibited tumor growth and showed a very low toxicity. Notably, the PT effect of Tpc-CuGd NPs not only promoted their tumor inhibitory capability but also significantly restricted the continued growth of the tumor after the discontinuation of the treatment. In addition, Tpc-CuGd significantly strengthened the T 1 -weighted signal of tumors and realized accurate cancer diagnosis. Therefore, this nanoplatform could be a great promising candidate for PT and chemodynamic synergistic theranostics.

Excessive iron ions in cancer cells can catalyze H 2 O 2 into highly toxic • OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the efficacy of the ferroptosis catalyst is still insufficient because of low Fe(II) release, which severely limited its application in clinic. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo- and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG-modified gadolinium engineering magnetic iron oxide-loaded Dox (ipGdIO-Dox). The introduction of the gadolinium compound disturbed the structure of ipGdIO-Dox, making the magnetic nanocatalyst be more sensitive to weak acid. When ipGdIO-Dox entered into cancer cells, abundant Fe(II) ions were released and then catalyzed H 2 O 2 into highly toxic OH • , which would elevate cellular oxidative stress to damage mitochondria and cell membranes and induce cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto the nanoplatform was also broken by high expression of GSH, and then, the Dox was released. This process not only effectively inhibited DNA replication but also further activated cellular ROS, making the nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery of ipGdIO-Dox significantly enhanced the T 1 - and T 2 -weighted MRI signal of the tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, ipGdIO-Dox might be a promising candidate for developing an MRI-guided chemo- and ferroptosis synergistic theranostic system.

We developed a cyclic amplification method for an organic afterglow nanoreporter for the real-time visualization of self-generated reactive oxygen species (ROS). We promoted semiconducting polymer nanoparticles (PFODBT) as a candidate for emitting near-infrared afterglow luminescence. Introduction of a chemiluminescent substrate (CPPO) into PFODBT (PFODBT@CPPO) resulted in a significant enhancement of afterglow intensity through the dual cyclic amplification pathway involving singlet oxygen ( 1 O 2 ). 1 O 2 produced by PFODBT@CPPO induced cancer cell necrosis and promoted the release of damage-related molecular patterns, thereby evoking immunogenic cell death (ICD)-associated immune responses through ROS-based oxidative stress. The afterglow luminescent signals of the nanoreporter were well correlated with light-driven 1 O 2 generation and anti-cancer efficiency. This imaging strategy provides a non-invasive tool for predicting the therapeutic outcome that occurs during ROS-mediated cancer therapy., (© 2021 Wiley-VCH GmbH.)

Chirality at different levels is widely observed in nature, but the clue to connect it all together, and the way chirality transfers among different levels are still obscure. Herein, a l-/d-lysine-based self-assembly system was constructed, in which two-step chirality transfer among three different levels was observed in aqueous solution. The chirality originated from the point chirality of amino acid derivatives l-/d-PyLys hydrochloride, and was transferred to the planar conformational chirality of water-soluble pillar[5]arene pR-/pS-WP5. Then, with the aid of pR-/pS-WP5, nanoparticles were formed that exhibited L-/R-handed circularly polarized luminescence with a dissymmetry factor of up to ±0.001, arising from pyrene chiral excimers. This multilevel chirality transfer not only provides a perspective to trace potential clues, and to pursue certain ways by which the chirality transfers, but also offers a strategy to create controllable CPL emission in aqueous media., (© 2021 Wiley-VCH GmbH.)

Combination chemotherapy with two or more complimentary drugs has been widely used for clinical cancer treatment. However, the efficacy and side effects of combination chemotherapy still remain a challenge. Here, we constructed an albumin-stabilized layered double hydroxide nanoparticle (BLDH) system to simultaneously load and deliver two widely used anti-tumor drugs, i.e. 5-fluorouracil (5FU) and albumin-bound PTX (Abraxane, ABX) for colorectal cancer treatment. The cellular uptake test has revealed that 5FU-ABX encapsulated BLDH (BLDH/5FU-ABX) nanoparticles were efficiently internalized by the colorectal cancer cell (HCT-116), synergistically inducing apoptosis of colon cancer cells. The in vivo test has demonstrated that BLDH/5FU-ABX nanomedicine significantly inhibited the tumor growth after three intravenous injections, without any detectable side effects. The enhanced therapeutic effectiveness is attributed to efficient accumulation of BLDH/5FU-ABX at tumor sites and acid-sensitive release of co-loaded drugs. Thus, combination chemotherapy based on BLDH/5FU-ABX nanomedicine would be a new strategy for colorectal cancer treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Menaquinone-7 is involved in bone metabolism and can be used to prevent and treat osteoporosis. However, as a fat-soluble vitamin, menaquinone-7 has poor water solubility. As a surfactant, hydrophobins can change the affinity/hydrophobicity of the covered interface. In this study, menaquinone-7 was modified by hydrophobins, and the different addition ratios were explored. Moreover, Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and water contact angle (WCA) measurements indicated that hydrophobins effectively bind to menaquinone-7 and greatly increase the hydrophilicity of the surface of menaquinone-7. Studies on the metabolism of MC3T3-E1 cells showed that compared with native menaquinone-7, HGFI-modified menaquinone-7 can significantly promote osteoblast differentiation but inhibit osteoclast differentiation. Besides, the Mito-Tracker Green experiments show that HGFI-modified menaquinone-7 can significantly promote the activity of mitochondria in cells. These findings indicate that hydrophobins can be used as an effective biomaterial to modify menaquinone-7, promote the formation of osteoblasts, and better to bone balance.

Lung metastasis is the principal reason for the majority of deaths from breast cancer. The nonsteroidal anti-inflammatory drug aspirin can prevent lung metastasis in breast tumors via inhibiting heparanase. However, the lack of specific targets and limited accumulation at the site of the tumor have thus far hindered the use of aspirin in oncotherapy. In this study, we developed the nanoplatform FA-BSA@DA and loaded it with the versatile aspirin prodrug DA to visualize and inhibit breast cancer metastasis via targeting heparanase. This nanosystem can be effectively targeted to folic acid (FA)-positive tumor cells, and would then subsequently release a high dose of DA, whose ester bond is specifically ruptured by H 2 O 2 in the tumor microenvironment to afford the therapeutic drug aspirin and near-infrared (NIR) fluorescent reporter DCM. The released aspirin can effectively prevent breast cancer lung metastasis through the inhibition of heparanase activity, and the NIR fluorescent signals emitted from DCM can be used to monitor and evaluate the metastasis levels of breast cancer. Our results showed that the expression of heparanase was significantly decreased, and lung metastasis from breast cancer was effectively monitored and inhibited after treatment with FA-BSA@DA. Furthermore, the collaborative therapy nanoplatform FA-BSA@DA/DOX exhibited strong therapeutic effects in the treatment of breast cancer in vitro and in vivo via the introduction of doxorubicin (DOX) to the system, which resulted in an even stronger result due to its synergistic effects with aspirin. This heparanase-reliant strategy has profound significance for the extended development of nanoplatforms based on versatile aspirin prodrugs, which may offer a solution to clinically prevent breast cancer recurrence and lung metastasis.

Silver (Ag) is released from a range of products and accumulates in agricultural soils as silver sulfide (Ag 2 S) through the application of Ag-containing biosolids as a soil amendment. Although Ag 2 S is comparatively stable, its solubility increases with salinity, potentially altering its impacts on microbial communities due to the anti-microbial properties of Ag. In this study, we investigated the impacts of Ag on the microbially mediated N cycle in saline soils by examining the relationship between the (bio)availability of Ag 2 S and microbial functioning following the application of Ag 2 S-containing sludge. Synchrotron-based X-ray absorption spectroscopy (XAS) revealed that the Ag 2 S was stable within the soil, although extractable Ag concentrations increased up to 18-fold in soils with higher salinity. However, the extractable Ag accounted for <0.05% of the total Ag in all soils and had no impact on plant biomass or soil bacterial biomass. Interestingly, at high soil salinity, Ag 2 S significantly increased cumulative N 2 O emissions from 80.9 to 229.2 mg kg -1 dry soil (by 180%) compared to the corresponding control sludge treatment, which was ascribed to the increased abundance of nitrification and denitrification-related genes (amoA, nxrB, narG, napA, nirS, and nosZ) and increased relative abundance of denitrifiers (Rhodanobacter, Salinimicrobium, and Zunongwangia). Together, our findings show that the application of Ag 2 S-containing sludge to a saline soil can disrupt the N cycle and increase N 2 O emissions from agroecosystems., 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 © 2020 Elsevier Ltd. All rights reserved.)

The accumulation of Ag 2 S in agricultural soil via application of Ag-containing sludge potentially affects the functioning of soil microorganisms and earthworms (EWs) due to the strong antimicrobial properties of Ag. This study examined the effects of Ag 2 S nanoparticles (Ag 2 S-NPs) on the EW-mediated ( Eisenia fetida and Pontoscolex corethrurus ) soil N cycle. We used 16S rRNA gene-based sequencing and quantitative polymerase chain reaction to examine the bacterial community and nitrification/denitrification-related gene abundance. The presence of either EWs or Ag significantly increased denitrification and N 2 O emissions. However, the addition of Ag 2 S to EW-inhabited soil reduced N 2 O emissions by 14-33%. Furthermore, Ag 2 S caused a low-dose stimulation but a high-dose inhibition to N 2 O flux from the EW gut itself. Accordingly, an increase in Ag in the EW gut caused a decrease in the relative abundance of denitrifiers in both the soil and the gut, especially for the dominant genus Bacillus . Ag 2 S also decreased the copy numbers of nitrification gene ( nxrB ) and denitrification genes ( napA , nirS , and nosZ ) in EW gut, leading to the observed decrease in N 2 O emissions. Collectively, applying Ag 2 S-containing sludge disturbs the denitrification function of the EW gut microbiota and the cycling of N in soil-based systems.

Hydrogen sulfide (H2S) as an important gaseous signaling molecule is closely related to numerous biological processes in living systems. To further study the physiological and pathological roles of H2S, convenient and efficient detection techniques for endogenous H2S in vivo are still in urgent demand. In this study, an electrochromic chromophore, dicationic 1,1,4,4-tetra-aryl butadiene (EM1), was innovatively introduced into upconversion nanoparticles (UCNPs) and a nanoprobe, PAAO-UCNPs-EM1, was constructed for the detection of H2S. This nanosystem was made of core-shell upconversion nanoparticles (NaYF4:Yb,Tm@NaYF4:Yb,Er), EM1, and polyacrylic acid (PAA)-octylamine. The EM1 with strong absorption ranging from 500 to 850 nm could serve as an energy acceptor to quench the upconversion luminescence of UCNPs through the Förster resonance energy transfer (FRET) process. In the presence of H2S, the EM1 in the nanoprobe was reduced to a colorless diene (EM2), resulting in the linear enhancement of luminescence emissions at 660 nm and 800 nm under the excitation of 980 nm light because the FRET was switched off. The nanoprobe PAAO-UCNPs-EM1PAAO-UCNPs-EM1 exhibited fast response and high sensitivity to H2S with a LoD of 1.21 × 10-7 M. Moreover, it was successfully employed in detecting the endogenous and exogenous H2S in living cells with high selectivity and low cytotoxicity. Also, this nanoprobe could distinguish normal and tumor cells by an upconversion luminescence imaging of endogenous H2S. Furthermore, the nanoprobe could significantly monitor H2S in a tumor-bearing nude mouse model. Therefore, we anticipate that this novel nanoprobe assembled with an electrochromic chromophore for responding to H2S and for bioimaging this molecule would have a promising prospect in biological and clinical investigations.

Based on the enhancement of synergistic antitumour activity to treat cancer and the correlation between inflammation and carcinogenesis, the authors designed chitosan nanoparticles for co-delivery of 5-fluororacil (5-Fu: an as anti-cancer drug) and aspirin (a non-steroidal anti-inflammatory drug) and induced synergistic antitumour activity through the modulation of the nuclear factor kappa B (NF-κB)/cyclooxygenase-2 (COX-2) signalling pathways. The results showed that aspirin at non-cytotoxic concentrations synergistically sensitised hepatocellular carcinoma cells to 5-Fu in vitro. It demonstrated that aspirin inhibited NF-κB activation and suppressed NF-κB regulated COX-2 expression and prostaglandin E2 (PGE2) synthesis. Furthermore, the proposed results clearly indicated that the combination of 5-Fu and aspirin by chitosan nanoparticles enhanced the intracellular concentration of drugs and exerted synergistic growth inhibition and apoptosis induction on hepatocellular carcinoma cells by suppressing NF-κB activation and inhibition of expression of COX-2.

Cancer starvation therapy based on catalytic chemistry of glucose oxidase (GOx) offers great potential for multimodal treatment, benefiting from both nutrition shutting-off and the oxidization product hydrogen peroxide (H 2 O 2 ). Herein, further optimization of such combined therapy was achieved by a cascade Nano-reactor, which was constructed by incorporating GOx into a bio-mimic upconversion nanosystem. The cascade began when GOx was delivered into tumor sites through homotypic targeting, facilitating selective starving of cancer cells and H 2 O 2 generation. Then, upon 980 nm laser excitation, the 470 nm light emitted by upconversion nanoparticles (NaYF 4 : Yb, Tm) photolyzed H 2 O 2 into hydroxyl radical for phototherapy, superior to direct photolysis by blue light with limited tissue penetration depth. Meanwhile, the 800 nm emission of UCNPs was used to track the in vivo fate and tumor targeting ability of the Nano-reactor. Radionuclide imaging further confirmed the targeting of the Nano-reactor to subcutaneous 4T1 tumor and lung metastasis. Significantly enhanced therapeutic efficacy of this cascade starvation-phototherapy was validated in vitro and in vivo, suggesting the Nano-reactor as a smart, simple and strong system for cancer multimodal therapy., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Arsenic trioxide (ATO) is effective in the treatment of hematological malignancies and solid tumors. However, its toxicity and side effects are severe, posing an obstacle in its clinical application. A controlled-release ATO carrier with mitochondrial targeting was constructed in this study. The safety and efficacy in vitro were investigated using a hemolysis test, cytotoxicity, proliferation, migration, apoptosis, and other changes in cell behavior. The safety and efficacy were further evaluated in vivo by hematoxylin-eosin staining, terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling staining, and blood testing in tumor-bearing mice. Immunohistochemically and western blotting experiments were conducted to explore the mechanism of combination therapy of material-based chemotherapy and microwave hyperthermia in vitro. We demonstrated that the nano-zirconia (ZrO 2 ) loading platform may be used to administer the ATO, with local precision-controlled release and mitochondrial targeting. Furthermore, we showed the safety of this approach for delivering high doses of ATO. In addition, we explored this new method in combination with in vitro microwave heat therapy, providing a potentially novel intravenous approach to chemotherapy. We described a new non-invasive treatment that improved the efficacy of ATO chemotherapy against hepatocellular carcinoma through nano-ZrO 2 carriers.

The responses of living cells to external mechanical and electrical stimulation play important roles in regulating their biological functions and behaviors, and the response mechanisms have attracted great attention. Global stimulation on cells is generally used in traditional methods, but it is insufficient to investigate the mechanism of a dynamic physiological response at the subcellular level. At present, there is still lack of a low-cost and easy-operated method to apply local mechanical force and electrical stimulation on living cells. In this study, an individual carbon nanocoil (CNC) is used as a microscale noninvasive tool for local stimulation on a single cell, and a living cell imaging technology, fluorescence resonance energy transfer (FRET), is adopted to determine the responses of cells. After demonstrating that CNCs have low cytotoxicity to be applied in the biological field, an individual CNC is used as a needle tip to apply local mechanical force on a single osteosarcoma cell, which is transfected with a Src FRET biosensor to explore the mechano-physiological response. A spatially increasing and polarized Src protein activation is observed on the stimulated cell. Moreover, a single CNC is also used as an electrode to exert periodic local electrical stimulation. Osteosarcoma cells transfected with calcium-FRET biosensors show notable spatial-polarized FRET emission ratio distribution, and the FRET ratio shows a recoverable tendency towards the initial state after withdrawing the electrical stimulation. The cell biofunctions and structures are not damaged during the experiment process, which indicates that CNC is a kind of non-invasive and bio-safe tip. The CNC tip is a powerful tool for exploring the mechanotransduction and electro-physiological characteristics of living cells.

Reactive oxygen species (ROS) with strong oxidizing and high activity have been regarded as an effective "weapon" for antitumor therapy, since it can induce organelle injury, oxidative damage, and cell death. Herein, hollow structured manganese carbonate (MnCO 3 ) nanocubes are fabricated and loaded with photosensitizer (chlorin e6, Ce6), obtaining a responsive nanoplatform H-MnCO 3 /Ce6-PEG (HMCP NCs). Two different approaches to upregulate intracellular ROS level were realized by HMCP NCs. On one hand, with irradiation of external laser, Ce6 could generate singlet oxygen ( 1 O 2 ) through a multistep photochemical process applied in photodynamic therapy (PDT). On the other hand, MnCO 3 could be specifically degraded into Mn 2+ in an acidic tumor microenvironment (TME), triggering Mn 2+ -activated Fenton-like reaction to convert endogenous H 2 O 2 into hydroxyl radical (•OH). In vitro combined chemodynamic therapy (CDT) and PDT showed that the metal ion-enhanced ROS production could break the intracellular redox equilibrium, thus leading to cell death. In vivo combined CDT/PDT with HMCP NCs exhibited remarkably enhanced therapeutic efficacy in inhibiting tumor growth, without resulting in noticeable damage to normal tissues. This work presents a unique type of manganese-based nanoplatform for efficiently generating ROS in solid tumors, favorable for ROS-involved therapeutic strategies.

To address the thereapeutic challenges in clinical cancer treatment and guarantee efficient and rapid intracellular delivery of drugs while evading efflux and chemotherapy resistance, herein, we designed a liposomal nanostructure equipped with superparamagnetic iron oxide nanoparticles (SPIOs) and anethole trithione (ADT, a hydrogen sulfide (H 2 S) donor drug). At first, by spatially focused manipulation of the external static magnetic field (SMF), the SPIOs and ADT-loaded liposomes (SPIOs-ADT-LPs) could rapidly overcome the cell membrane barrier to enter the cytoplasm, which could be imaged by magnetic resonance imaging (MRI). Sequentially, the intracellular release of ADT drugs was triggered by enzymatic catalysis to generate acoustic-sensitive H 2 S gas. At the beginning, during the production of H 2 S at low concentrations, the cell membrane could be permeabilized to further increase the cellular uptake of SPIOs-ADT-LPs. The continued generation of H 2 S gas bubbles, imaged by ultrasound (US) imaging, further enhanced the intracellular hydrostatic pressure (above 320 pN per cell) to physically unfold the cytoskeleton, leading to complete cell death. The magneto-acoustic approach based on SPIO-ADT-LPs as intracellular bubble reactors leads to improved anticancer cell efficacy and has potential applications for novel MRI/US dual image-guided bubble bursting of cancer cells.

Hypoxia, as a characteristic feature of solid tumor, can significantly adversely affect the outcomes of cancer radiotherapy (RT), photodynamic therapy, or chemotherapy. In this study, a strategy is developed to overcome tumor hypoxia-induced radiotherapy tolerance. Specifically, a novel two-dimensional Pd@Au bimetallic core-shell nanostructure (TPAN) was employed for the sustainable and robust production of O 2 in long-term via the catalysis of endogenous H 2 O 2 . Notably, the catalytic activity of TPAN could be enhanced via surface plasmon resonance (SPR) effect triggered by NIR-II laser irradiation, to enhance the O 2 production and thereby relieve tumor hypoxia. Thus, TPAN could enhance radiotherapy outcomes by three aspects: 1) NIR-II laser triggered SPR enhanced the catalysis of TPAN to produce O 2 for relieving tumor hypoxia; 2) high-Z element effect arising from Au and Pd to capture X-ray energy within the tumor; and 3) TPAN affording X-ray, photoacoustic, and NIR-II laser derived photothermal imaging, for precisely guiding cancer therapy, so as to reduce the side effects from irradiation., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, magnetic humic acid (MHA) nanoparticle was prepared and confirmed the enhancement on reduction of azo dyes under high salt concentration. The anaerobic growth of the strain Bacillus sp. on quinones makes the biogenic hydroquinone feasible, and the latter was proven to reduce the azo dyes stoichiometrically. This in-situ reversibly oxidation and reduction of MHA acts as electron shuttle to catalyze the biotic reduction of the azo dyes. The biodegradation efficiencies in batch experiments and sequencing batch reactor with MHA were increased by 1.5-2.5 times as compared to that of control without the catalyzer. Moreover, the negligible leaching of HA under various environmental conditions suggests the robustness of the coating of HA on Fe/O surface. These results indicated that the as-prepared MHA could be used as redox mediator to accelerate the extracellular electron transfer, which is of great environmental significance for the removal of hazardous compounds., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Developing new strategies to alleviate tumor hypoxia and enhance the therapeutic efficacy towards solid tumors is of great significance to tumor therapy. Herein, to overcome tumor hypoxia, specifically designed aza-BODIPY photosensitizer is co-loaded with anti-cancer drug (doxorubicin, DOX) onto the hydrangea-structured MnO 2 nanoparticles, and a tumor microenvironment (TME) responsive degradable nanoplatform (MDSP NP) is established. MDSP NPs (∼54 nm), with near infrared absorption (∼853 nm), can be rapidly dissociated to generate oxygen in response to TME, whereby improving tumor hypoxia, in favor of effective drugs release and enhanced chemo/photodynamic therapy. Revealed by in vivo fluorescence and photoaccoustic imaging, MDSP NPs are preferential accumulated at tumor site. Confirmed by photothermal imaging, MDSP NPs can induce hyperthermia to relieve hypoxia, promote the uptake of therapeutic nanoparticles, and further reduce the resistance and improve the therapeutic efficiency. As a result, a remarkable synergistic tumor chemo/photodynamic/photothermal therapy with hydrangea-structured TME responsive oxygen-self-generation nanoplatform is confirmed by both in vitro and in vivo studies, testifying its great potential for hypoxic tumor treatment in clinical application., (Copyright © 2019. Published by Elsevier Ltd.)

A hexagonal FeSe nanoparticle anode with a novel reaction mechanism and mechanical stability may fully facilitate the desirable rate capability and cycling performance in sodium-ion batteries. In situ TEM reveals that hexagonal FeSe nanoparticle transition to the Fe and Na2Se phase during sodiation, while the products transform to the tetragonal FeSe phase after desodiation.

Two-photon fluorescent imaging that utilizes two near-infrared photons as an excitation source affords higher penetration depth of tissue for biomedical research, compared with one-photon fluorescent imaging. However, the high laser power levels of the excitation source may induce photobleaching of two-photon dyes and photodamage to biosamples, which hampers its wide application for in vivo imaging. Inspired by supramolecular chemistry, we have developed a two-photon excited nanoprobe (TPFN) via host-guest interaction with excellent sensitivity, selectivity, biocompatibility, water solubility, and imaging penetration depth. Notably, this supramolecular assembly can significantly amplify the fluorescence intensities of guest molecules (21-fold increase), thereby affording a detection limit of 0.127 μM for sensing H 2 O 2 , which is greatly lower than that of free guest molecules (11.98 μM). In particular, ratiometric fluorescent imaging provides more accurate analysis of intracellular H 2 O 2 via the built-in correction of the internal reference. Importantly, TPFN excited by a two-photon laser provides higher penetration depth for visualizing H 2 O 2 in deeper liver tissues, compared with that of one-photon excitation. Thus, TPFN can serve as a powerful nanoplatform for ratiometric imaging of various species via this facile supramolecular self-assembly strategy.

Photoactivated therapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a spatiotemporally precise, controllable, and noninvasive method for tumor therapy and has therefore attracted increasing attention in recent years. However, it is still a challenge to obtain highly efficient therapeutic photoactive agents (PAAs) and deliver them into tumor, especially the core of solid tumors. Here, we have developed a newly engineered monocyte (MNC)-based PAA system that realizes precise and highly efficient tumor diagnosis and therapy. First, a near-infrared emissive PAA molecule with both strong singlet oxygen ( 1 O 2 ) production and high photothermal conversion efficiency was precisely designed for realizing simultaneous PDT and PTT of tumor and was further fabricated to form PAA nanoparticles (NPs). After loading the PAA NPs into MNCs, the MNCs were then decorated with cyclic Arg-Gly-Asp (cRGD) groups through a metabolic labeling method to further improve their ability of targeting and homing into the deep regions of tumors. Using this strategy, we have achieved highly efficient solid tumor ablation results both in vitro and in vivo, indicating that our strategy has a promising prospect for solid tumor therapy.

We present the design of antifouling zwitterion-functionalized manganese oxide (Mn 3 O 4 ) nanoparticles (NPs) modified with folic acid (FA) for targeted tumor magnetic resonance (MR) imaging. In the current work, diethylene glycol-stabilized Mn 3 O 4 NPs were initially prepared via a solvothermal approach, coated with polydopamine (PDA), fluorescently labeled with rhodamine B, conjugated with FA via amide bond formation, and finally covered with zwitterions of l-lysine (Lys). The thus-generated multifunctional Mn 3 O 4 NPs display excellent water dispersibility and colloidal stability, good protein resistance ability, and desirable cytocompatibility. With the PDA and Lys modifications, the multifunctional Mn 3 O 4 NPs own an ultrahigh r 1 relaxivity (89.30 mM -1 s -1 ) and enable targeted tumor MR imaging, owing to the linked FA ligands. The designed antifouling zwitterion-functionalized Mn 3 O 4 NPs may be employed as an excellent MR contrast agent for targeted MR imaging of other biological systems.

The exorbitant level of hydrogen peroxide is closely related to many human diseases. The development of novel probes for H 2 O 2 detection will be beneficial to disease diagnosis. In this study, a novel Nd 3+ -sensitized upconversion nanoprobe based on Förster resonance energy transfer was first developed for sensing H 2 O 2 . This nanosystem was made of core-shell upconversion nanoparticles (emission at 540 and 660 nm), dicyanomethylene-4 H-pyran (DCM)-H 2 O 2 , and poly acrylic acid (PAA)-octylamine. Obviously, upconversion nanoparticles (UCNPs) doped with Nd 3+ acted as an energy donor, and DCM-H 2 O 2 , transferring to DCM-OH with the reaction of H 2 O 2 , acted as an energy acceptor. The ratiometric upconversion luminescence (540 nm/660 nm) signal could be utilized to visualize the H 2 O 2 level, and the LOD of the nanoprobe for H 2 O 2 was quantified to be 0.168 μM. Meanwhile, owing to the dope of Nd 3+ , the nanoprobe would not induce the overheating effect in biological samples and could possess deeper tissue penetration depth, compared with the UCNPs excited by 980 nm light during bioimaging. The nanoprobe could also play an important role in detecting the exogenous and endogenous H 2 O 2 in living cells with ratiometric UCL (upconversion luminescence) imaging. Furthermore, our nanoprobe could function in detecting the H 2 O 2 in a tumor-bearing mouse model. Therefore, this novel nanoprobe along with the ratiometric method for responding and bioimaging H 2 O 2 could serve as a new model that promotes the emergence of novel probes for H 2 O 2 detection.

Purpose: Electrospun scaffolds have been studied extensively for their potential use in bone tissue engineering. However, their hydrophobicity and relatively low matrix stiffness constrain their osteoinduction capacities. In the present study, we studied polymer electrospun scaffolds coated with hydrophilic hematite nanoparticles (αFeNPs) constructed using layer-by-layer (LbL) assembly to construct a bioactive interface between the scaffolds and cells, to improve the osteoinduction capacities of the scaffolds., Materials and Methods: The morphology of the αFeNPs was assessed. Surface properties of the scaffolds were tested by X-ray photoelectron spectroscopy (XPS), surface water contact angle, and in vitro protein adsorption test. The stiffness of the coating was tested using an atomic force microscope (AFM). In vitro cell assays were performed using rat adipose-derived stem cells (ADSCs)., Results: Morphology characterizations showed that αFeNPs assembled on the surface of the scaffold, where the nano assemblies improved hydrophilicity and increased surface roughness, with increased surface stiffness. Enhanced initial ADSC cell spread was found in the nano assembled groups. Significant enhancements in osteogenic differentiation, represented by enhanced alkaline phosphatase (ALP) activities, elevated expression of osteogenic marker genes, and increased mineral synthesis by the seeded ADSCs, were detected. The influencing factors were attributed to the better hydrophilicity, rougher surface topography, and harder interface stiffness. In addition, the presence of nanoparticles was believed to provide better cell adhesion sites., Conclusion: The results suggested that the construction of a bioactive interface by LbL assembly using αFeNPs on traditional scaffolds should be a promising method for bone tissue engineering., Competing Interests: Disclosure The authors report no conflicts of interest in this work.