Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual impairment.The incidence of DED is gradually increasing with the highfrequency use of electronic products.Although inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROS)play a pivotal role in the vicious cycle by regulating inflammation from upstream.Therefore,current therapies merely targeting inflammation show the failure of DED treatment.Here,a novel dual-atom nanozymes(DAN)-based eye drops are developed.The antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic polymer.The in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROS,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell apoptosis.Consequently,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious cycle.Our findings open an avenue to make the DAN as an intervention form to DED and ROSmediated inflammatory diseases.

Reduction-sensitive nanomicelles:Delivery celastrol for retinoblastoma cells effective apoptosis

Celastrol,a Chinese herbal medicine,has exhibited anticancer activity in many types of cancer cells.However,the further clinical application of celastrol is restricted by its poor water solubility and serious side effects.Furthermore,the apoptosis mechanism of tumor cells induced by celastrol has not been exhausted yet.In this study,we developed a reduction sensitive polymeric vector for tumor-targeted celastrol delivery.And our researches indicated that the celastrol could be delivered by reductionsensitive nanomedicine(RSNMs)with a controlled release strategy.Meanwhile,the cell uptake results indicated that excellent reduction-sensitive behavior of RSNMs could effectively accelerate celastrol into the human retinoblastoma(RB)cell.The cell cytotoxicity assay demonstrated that celastrol inhibited proliferation of human RB Y79 cells growth in a dose-dependent manner.Furthermore,the results of flow cytometry and terminal dUTP nick-end labeling(TUNEL)staining showed that celastrol induced apoptosis of the RB Y79 cells,and revealed a time-dependent increase in apoptosis induction of RB Y79 cells.The results of western blotting showed that celastrol induced the apoptosis of human RB Y79 cells involving the activation of caspase-3 and caspase-9.In conclusion,our results revealed that RSNMs may be utilized as a novel therapy for retinoblastoma.

Ca^(2+)-supplying black phosphorus-based scaffolds fabricated with microfluidic technology for osteogenesis

Effective osteogenesis remains a challenge in the treatment of bone defects.The emergence of artificial bone scaffolds provides an attractive solution.In this work,a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus(P),calcium(Ca),and silicon(Si).We developed black phosphorus(BP)-based,three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment.The fibrous scaffolds were fabricated from 3D poly(L-lactic acid)(PLLA)nanofibers(3D NFs),BP nanosheets,and hydroxyapatite(HA)-porous SiO2 nanoparticles.The 3D BP@HA NFs possess three advantages:i)stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells(BMSCs)into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis;ii)plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area;iii)the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation,thus achieving accelerated osteogenesis.Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs,with the assistance of NIR laser,exhibited good performance in promoting bone regeneration.Furthermore,microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs,rapid processing,high throughput and mass production,greatly improving the prospects for clinical application.This is also the first BP-based bone scaffold platform that can self-supply Ca^(2+),which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.

Green rapid synthesis of Cu_(2)O/Ag heterojunctions exerting synergistic antibiosis

Semiconductor-noble metal composite has become a research focus due to its superior performance compared with its respective component.Although various methods have been developed to synthesize semiconductor-noble metal heterostructures,most of them are relatively complex multistep and use toxic reactants of high cost and risk.In this work,a series of Cu_(2)O/Ag heterojunctions were quickly prepared in one step via simple microwave-assisted green route.XRD,SEM,TEM,EDS,XPS,etc.were used to characterize obtained products,and the results indicate a Cu_(2)O/Ag metal-semiconductor heterojunction in micro-nano size was fabricated successfully.In addition,antibacterial behavior of Cu_(2)O/Ag heterojunctions against E.coli and S.aureus were investigated.Owing to the synergistic effect of Cu_(2)O and Ag,the heterojunction exhibits much better antibacterial performance than the pristine Cu_(2)O does.This work provides new insights into the green design and fabrication of surface-modified Cu_(2)O hybrid multifunctional materials for antibacterial applications.

Size engineering of 2D MOF nanosheets for enhanced photodynamic antimicrobial therapy

Although porphyrin-based metal-organic frameworks(MOFs)have been widely explored as photosensitizers for photodynamic therapy,how the size will affect the light-induced catalytic activity for generation of reactive oxygen species(ROS)still remain unclear.Herein,we first report the size-controlled synthesis of two-dimensional(2D)porphyrin-based PCN-134 MOF nanosheets by a two-step solvothermal method to explore the size effect on its PDT performance,thus yielding enhanced photodynamic antimicrobial therapy.By simply controlling the reaction temperature in the synthesis process,the bulk PCN-134 crystal,large PCN-134(L-PCN-134)nanosheets with a lateral size of 2–3μm and thickness of 33.2–37.5 nm and small PCN-134 nanosheets(S-PCN-134)with a lateral size of 160–180 nm and thickness of 9.1–9.7 nm were successfully prepared.Interestingly,the S-PCN-134 nanosheets exhibit much higher photodynamic activity for ROS generation than that of the bulk 3D PCN-134 crystal and L-PCN-134 nanosheets under a660 nm laser irradiation,suggesting that the photodynamic activity of PCN-134 MOF increases when the size reduces.Therefore,the S-PCN-134 nanosheets show much enhanced performance when used as a photosensitizer for photodynamic antimicrobial activity and wound healing.

Converting ultrafine silver nanoclusters to monodisperse silver sulfide nanoparticles via a reversible phase transfer protocol

To achieve better control of the formation of silver sulfide （Ag2S） nanoparticles, ultrasmall Ag nanoclusters protected by thiolate ligands （Ag44（SR）30 and Agla（GSH）9） are used as precursors, which, via delicate chemistry, can be readily converted to monodisperse Ag2S nanoparticles with controllable sizes （4-16 nm） and switchable solvent affinity （between aqueous and organic solvents）. This new synthetic protocol makes use of the atomic monodispersity and rich surface chemistry of Ag nanoclusters and a novel two-phase protocol design, which results in a well-controlled reaction environment for the formation of Ag2S nanopartides.

Activating MoO_(3) nanobelts via aqueous intercalation as a near-infrared type I photosensitizer for photodynamic periodontitis treatment

Although molybdenum trioxide nanomaterials have been widely explored as nanoagents for biomedical applications against bacteria through photothermal therapy,chemodynamic therapy,and catalytic therapy,their utilization as photosensitizers for photodynamic therapy(PDT)have been rarely reported so far.Herein,we report the activation of MoO_(3) nanobelts via aqueous co-intercalation of Na+and H_(2)O into their van der Waals gaps as a near-infrared Type I photosensitizer for photodynamic periodontitis treatment.The Na^(+)/H_(2)O intercalation of MoO_(3) nanobelts can shorten its length,generate rich oxygen vacancies,and enlarge its interlayer gaps.Such structural changes thus can induce the color change from white to dark blue with a strong near-infrared(NIR)absorption.When used as a photosensitizer,the I-MoO_(3−x) nanobelts exhibit much higher activities for the generation of superoxide radical(·O_(2)^(−))under an 808 nm laser irradiation than that of the pristine MoO_(3) nanobelts.Therefore,the prepared I-MoO_(3)−x nanobelts show a spectral antibacterial activity against Escherichia coli and Saccharomyces aureus,thus yielding a good clinical therapeutic effect on periodontitis.Our study proves that aqueous intercalation can be a simple but powerful strategy to activate layered MoO_(3) nanomaterials for high-performance PDT.