Corrigendum to "Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment" [Bioact. Mater. 18C (2022) 1-14].

[This corrects the article DOI: 10.1016/j.bioactmat.2022.02.017.].

Nanosizing Coamorphous Drugs Using Top-Down Approach: The Effect of Particle Size Reduction on Dissolution Improvement.

Nanotechnology and coamorphous are both advanced technologies that can effectively improve the solubility of drugs. This study has been the first attempt to combine these two approaches to construct the coamorphous nanoparticles to improve the dissolution and investigated the effect of physical properties of coamorphous solid on the nanosizing process. Two types of coamorphous solid, i.e., curcumin-artemisinin and quercetin-lysine, were selected as models. Coamorphous curcumin-artemisinin could highly contribute to the size reduction during milling compared to the crystalline form, which might attribute to the change of crystallinity. Nanosized coamorphous curcumin-artemisinin showed higher dissolution than nanocrystals and single coamorphous sample. However, quercetin-lysine coamorphous nanoparticles did not reflect significant dissolution improvement compared with the microsized sample. The difference of initial dissolutions for both could be the main reason. The directly mixing and drying method was confirmed to be an effective and simple approach to maintain the dissolution of nanosized coamorphous sample.

Mesoporous Calcium-Silicate Nanoparticles Loaded with Prussian Blue Promotes Enterococcus Faecalis Ferroptosis-Like Death by Regulating Bacterial Redox Pathway ROS/GSH.

Background: Mesoporous calcium-silicate nanoparticles (MCSNs) are advanced biomaterials that have been used to control drug delivery for many years. Ultrasmall Prussian blue nanoparticles (UPBNPs) showed high peroxidase and catalase-like activities. This study evaluated the antibacterial and antibiofilm properties, mechanism and cytotoxicity of UPBNPs-MCSNs composites synthesized by both as precursors. Methods: UPBNPs-MCSNs were prepared and characterized. The antibacterial effect of UPBNPs-MCSNs was evaluated by the MTT assay and CFU counting method, and their biosafety was tested by CCK8. Then explore the antibacterial mechanism, including TEM observation of bacterial morphology, and detection of bacterial ROS, LPO and GSH levels. The antibiofilm activity of UPBNPs-MCSNs was tested by E. faecalis biofilm model in human roots. The roots were pretreated with materials and cultured with E. faecalis, and the survival of E. faecalis on the root canal wall was observed by SEM and CLSM. Results: The results showed that UPBNPs-MCSNs had potent antibacterial and antibiofilm activities. They can aggregate on the dentin surface and significantly inhibit E. faecalis adhesion and colonization. Their antibacterial activity is as effective as NaClO and calcium hydroxide (CH), can significantly prolong the time of bacterial colonization than CH, but have lower cytotoxicity to normal cells. We found that UPBNPs-MCSNs trigger a like classic ferroptosis pathway in bacteria. UPBNPs-MCSNs can induce bacteria to produce ROS and LPO, and reduce GSH level. Moreover, we observed that the metal ions chelator and the antioxidant could block their antibacterial activity. Conclusion: These results reveal that UPBNPS-MCSNs have high antibacterial and antibiofilm, and can mediate the bacterial redox pathway ROS/GSH like the classical pathway of ferroptosis, providing a theoretical basis for them to develop into a safe and effective novel root canal disinfectant.

Correction: Ultrasmall Prussian blue nanoparticles attenuate UVA-induced cellular senescence in human dermal fibroblasts via inhibiting the ERK/AP-1 pathway.

Correction for 'Ultrasmall Prussian blue nanoparticles attenuate UVA-induced cellular senescence in human dermal fibroblasts via inhibiting the ERK/AP-1 pathway' by Yueyue Li et al., Nanoscale, 2021, 13, 16104-16112, https://doi.org/10.1039/D1NR04268H.

Temperature-Dependent CAT-Like RGD-BPNS@SMFN Nanoplatform for PTT-PDT Self-Synergetic Tumor Phototherapy.

Phototherapies such as photothermal therapy (PTT) and photodynamic therapy (PDT) are considered as alternatives for tumor remedies, because of their advantages of precise spatial orientation, minimally invasive, and nonradiative operation. However, most of phototherapeutic agents still suffer from low photothermal conversion efficacy and photodynamic performance, poor biocompatibility, and intratumor accumulation. Herein a biocompatible and target-deliverable PTT-PDT self-synergetic nanoplatform of RGD-BPNS@SMFN based on temperature-dependent catalase (CAT)-like behavior for tumor elimination is presented. The homogeneously dispersible nanoplatform is designed and fabricated through anchoring spherical manganese ferrite nanoparticles (SMFN) to black phosphorus nanosheets (BPNS), followed by arginine-glycine-aspartic acid (RGD) peptide modification. The nanoplatform exhibits excellent targeting ability and enhanced photonic response in comparison to plain BPNS and SMFN in vitro and in vivo. It is found that PTT and PDT have a self-synergetic behavior by means of the dual phototherapy mode interaction. The self-synergetic mechanism is mainly ascribed to PTT-promoted inherent CAT-like activity in the nanoplatform, which remodels the tumor hypoxia microenvironment and further ameliorates the PDT efficiency, providing promising high performance nanoplatform for synergetic dual mode phototherapy, enriching the design for the antitumor nanozyme.

Ultrasmall Prussian blue nanoparticles attenuate UVA-induced cellular senescence in human dermal fibroblasts via inhibiting the ERK/AP-1 pathway.

Ultraviolet A (UVA) irradiation can induce cellular senescence and cause skin photoaging, which is mainly driven by the excessive production of reactive oxygen species (ROS). Emerging studies have focused on new strategies for the prevention of skin photoaging. Ultrasmall Prussian blue nanoparticles (USPBNPs) demonstrate an intensive ability to scavenge ROS as nanozymes and exhibit great potential in the treatment of ROS-related diseases. Our goal was to investigate the anti-senescent role of USPBNPs against UVA-induced premature senescence in human dermal fibroblasts (HDFs). Our results showed that the activation of senescence-associated ß-galactosidase (SA-ß-gal) and the arrest of the cell cycle induced by UVA radiation in HDFs were significantly inhibited by pretreatment of USPBNPs (1 µg ml-1). Furthermore, USPBNPs downregulated the expression of DNA damage marker γH2AX and inhibited the secretion of senescence-associated secretory phenotypes (SASP) including IL-6, TNF-α and matrix metalloproteinases (MMPs). In addition, we found that the antiphotoaging effect of USPBNPs involved the scavenging of ROS as well as the inhibition of the ERK/AP-1 pathway. In conclusion, USPBNPs exhibited great potential to become novel anti-photoaging agents by alleviating UVA-induced cellular senescence and thus delaying the process of skin photoaging.

Cardamine hupingshanensis aqueous extract improves intestinal redox status and gut microbiota in Se-deficient rats.

BACKGROUND: As an essential trace element for mammalian species, selenium (Se) possesses powerful antioxidant properties and is a potential regulator of intestinal microbiota. However, effects of Cardamine hupingshanensis aqueous extract (CE), rich in Se, on balancing the intestinal redox status and regulating gut microbiota have been neglected. RESULTS: An Se-deficient rat model was established by feeding a low-Se diet (LD) for 5 weeks and CE was then supplemented to LD or normal-Se-diet (ND) rats. Antioxidant enzyme activities and short-chain fatty acids (SCFA) concentration were increased by CE in both LD and ND rats. CE improved the intestinal morphology of LD rats impaired by deficient Se. Intestinal microbiota demonstrated various changes; for example, Butyrivibrio was increased in LD rats, while Bacteroides, Christensenellaceae, Clostridiaceae and Blautia were enhanced in ND rats. CONCLUSION: Our findings provide evidence that CE shows potential in improving intestinal redox status and regulating gut microbiota. © 2020 Society of Chemical Industry.

Achieving Ultrasmall Prussian Blue Nanoparticles as High-Performance Biomedical Agents with Multifunctions.

Prussian blue nanoparticles (PBNPs), which belong to the iron-based metal-organic frameworks, are important biomedical agents. Reducing the size of PBNPs can bring improved functional properties, but unfortunately, has been a long-standing challenge. Herein, sub-5 nm ultrasmall PBNPs (USPBNPs) were successfully synthesized by using ethanol/water mixture as the solvent and polyvinyl pyrrolidone (PVP) as the surface capping agent. Adjusting the ethanol/water ratio is not only able to control the nucleation time and size of PBNPs but also tune the conformation of PVP molecules so as to prevent interparticle attachment and enlargement. At an ethanol/water ratio of 3:1, highly stable USPBNPs with a size of ∼3.4 nm were synthesized. Due to their large specific surface area, they demonstrated high peroxidase-like and catalase-like activities, which outperform PBNPs synthesized by a conventional method. In addition, they also showed a high longitudinal relaxation rate (r1) of 1.3 mM-1 S-1, suggesting their potential to be used as T1 MRI agent.

Indocyanine Green Assembled Nanobubbles with Enhanced Fluorescence and Photostability.

Indocyanine green (ICG) is a near-infrared (NIR) fluorescent dye for extensive biomedical application. However, its fluorescence intensity is limited by its poor aqueous stability and concentration-dependent aggregation. To overcome these limitations, ICG self-assembled nanobubbles (ICG-NBs) with an average size of 244.6 nm are fabricated. In the ICG-NB assembled structures, the ICG molecules are arrayed on the gas-liquid interface by the hydrophobic interaction with the gas core and hydrophilic heads with water. Results show that ICG-NBs exhibited good monodispersity and excellent fluorescence and size stability. Compared with ICG solution, the ICG-NBs indicate the enhanced quantum yield and fluorescence intensity. The surface-enhanced Raman scattering (SERS) spectra and fluorescence lifetime measurement demonstrate that the ICG molecule assembled NBs could result in the changes of molecular vibration and time-resolved intensity decays of ICG. Thus, the ICG-NBs could be more beneficial for optical imaging in clinical applications in the future.

Moderate cooling coprecipitation for extremely small iron oxide as a pH dependent T1-MRI contrast agent.

Iron based nanomedicine (IBNM) has been one powerful diagnostic tool as a magnetic resonance imaging (MRI) contrast agent (CA) in the clinic for years. Conventional IBNMs are generally employed as T2-MRI CAs, but most of them are constrained in clinical indication expansion by magnetic susceptibility artifacts. In comparison, extremely small iron oxide (ESIO) with a core size less than 5 nm has demonstrated the T1-MRI effect, which provides prospects for a Gd-based agent alternative. Nevertheless, currently developed ESIOs for T1-MRI CAs always require harsh conditions such as a high temperature and high boiling point reagent. Moreover, very few of the currently developed ESIOs meet the stringent pharmaceutical standard. Herein, on the basis of a crystal nuclear precipitation-dissolution equilibrium mechanism and outer/inner sphere T1-MRI theory, monodisperse ESIOs with an average size of 3.43 nm (polydispersity index of 0.104) are fabricated using a moderate cooling procedure with mild coprecipitation reaction conditions. The as-synthesized ESIOs display around 3-fold higher T1 MRI signal intensity than that of commercial Ferumoxytol (FMT), comparable to that of Gd-based CAs in vitro. Additionally, the T1-MRI performance of the ESIOs is pH dependent and delivers bright signal augmentation. Eventually, the internalization into mesenchymal stem cells of the ESIO is realized in the absence of a transferring agent. Considering the identical structure and composition of the ESIOs as compared to that of FMT, they could meet the pharmaceutical criteria, thus providing great potential as T1-MRI Cas, for instance as stem cell tracers.

Magnetic internal heating-induced high performance Prussian blue nanoparticle preparation and excellent catalytic activity.

A magnetic internal heating single-precursor approach was exploited to fabricate higher quality Prussian blue nanoparticles (PBNPs) with excellent crystallinity, dispersibility and uniformity. Furthermore, the magnetic properties and MRI contrast effect were improved. Subsequently, significantly increased nanoenzyme activity has been demonstrated.

Progress in Applications of Prussian Blue Nanoparticles in Biomedicine.

Prussian blue nanoparticles (PBNPs) with favorable biocompatibility and unique properties have captured the attention of extensive biomedical researchers. A great progress is made in the application of PBNPs as therapy and diagnostics agents in biomedicine. This review begins with the recent synthetic strategies of PBNPs and the regulatory approaches for their size, shape, and uniformity. Then, according to the different properties of PBNPs, their application in biomedicine is summarized in detail. With modifiable features, PBNPs can be used as drug carriers to improve the therapeutic efficacy. Moreover, the exchangeable protons and adsorbability enable PBNPs to decontaminate the radioactive ions from the body. For biomedical imaging, photoacoustic and magnetic resonance imaging based on PBNPs are summarized, as well as the strategies to improve the diagnostic effectiveness. The applications related to the photothermal effects and nanoenzyme activities of PBNPs are described. The challenges and critical factors for the clinical translation of PBNPs as multifunctional theranostic agents are also discussed. Finally, the future prospects for the application of PBNPs are considered. The aim of this review is to provide a better understanding and key consideration for rational design of this increasingly important new paradigm of PBNPs as theranostics.

Ferumoxytol of ultrahigh magnetization produced by hydrocooling and magnetically internal heating co-precipitation.

Ferumoxytol, which is originally intended for MRI and anemia treatment, is currently the only inorganic nanodrug approved by FDA for clinical application in vivo. Common ferumoxytol seems incapable of meeting the requirements for diverse applications. Thus, the development of a novel strategy based on co-precipitation to produce ferumoxytol with high quality is an imminent task. Herein, we proposed a physically assisted strategy, namely hydrocooling and magnetically internal heating co-precipitation, to optimize the properties of ferumoxytol and thus significantly enhance its magnetic performance. Magnetization of the newly developed ferumoxytol can reach 104-105 emu g-1 Fe, which is the highest value among the reported results. It has been found that the crystalline structures of the newly developed ferumoxytol have been greatly improved on the basis of pharmaceutical quality criteria.

Sinapultide-loaded lipid microbubbles and the stabilization effect of sinapultide on the shells of lipid microbubbles.

Microbubbles (MBs) hold promise in various biomedical applications due to their ultrasound-responsive properties. However, the stability and contrast enhancement duration of gas encapsulated MBs are still challenging. The aim of this study is to fabricate novel sinapultide (a synthetic pulmonary surfactant) stabilized MBs as ultrasound contrast agents. The optimized MBs generated from a mixture of phospholipid components and sinapultide have an average diameter of 1.82 ± 0.15 µm and a zeta potential of -55.2 ± 3.9 mV. Over 95% of the MBs have a mean diameter of less than 8 µm, indicating that the appropriately sized MBs can be applied as ultrasound contrast agents used in clinic. Furthermore, the interaction between sinapultide and lipid molecules and the stabilization mechanism of sinapultide on the shells of MBs were investigated by molecular dynamics simulation. The results demonstrate that the stability of MBs was increased effectively when the appropriate amount of sinapultide was added due to the decrease of surface tension. Accordingly, acoustic accumulation imaging analysis in vitro indicates that stable gas encapsulated sinapultide loaded MBs can provide a high scattering intensity resulting in better echogenicity. And the optimized concentration of sinapultide-loaded MBs can improve the contrast enhancement effect obviously compared with non-sinapultide MBs. Therefore, sinapultide-loaded lipid MBs may be designed as novel ultrasound contrast agents and used for clinical application in the future.