Co-delivery of retinoic acid and miRNA by functional Au nanoparticles for improved survival and CT imaging tracking of MSCs in pulmonary fibrosis therapy

Mesenchymal stem cells(MSCs)have emerged as promising candidates for idiopathic pulmonary fibrosis(IPF)therapy.Increasing the MSC survival rate and deepening the understanding of the behavior of transplanted MSCs are of great significance for improving the efficacy of MSC-based IPF treatment.Therefore,dual-functional Au-based nanoparticles(Au@PEG@PEI@TAT NPs,AuPPT)were fabricated by sequential modification of cationic polymer polyetherimide(PEI),polyethylene glycol(PEG),and transactivator of transcription(TAT)penetration peptide on AuNPs,to co-deliver retinoic acid(RA)and microRNA(miRNA)for simultaneously enhancing MSC survive and real-time imaging tracking of MSCs during IPF treatment.AuPPT NPs,with good drug loading and cellular uptake abilities,could efficiently deliver miRNA and RA to protect MSCs from reactive oxygen species and reduce their expression of apoptosis executive protein Caspase 3,thus prolonging the survival time of MSC after transplantation.In themeantime,the intracellular accumulation of AuPPT NPs enhanced the computed tomography imaging contrast of transplantedMSCs,allowing them to be visually tracked in vivo.This study establishes an Au-based dual-functional platform for drug delivery and cell imaging tracking,which provides a new strategy for MSC-related IPF therapy.

Controlled synthesis of porous spinel cobalt manganese oxides as efficient oxygen reduction reaction electrocatalysts

In this article, we report a facile precursor pyrolysis method to prepare porous spinel-type cobalt manganese oxides （CoxMng-xO4） with controllable morphologies and crystalline structures. The capping agent in the reaction was found to be crucial on the formation of the porous spinel cobalt manganese oxides from cubic Co2MnO4 nanorods to tetragonal CoMn2O4 microspheres and tetragonal CoMn204 cubes, respectively. All of the prepared spinel materials exhibit brilliant oxygen reduction reaction （ORR） electrocatalysis along with high stability. In particular, the cubic Co2MnO4 nanorods show the best performance with an onset potential of 0.9 V and a half-wave potential of 0.72 V which are very close to the commercial Pt/C. Meanwhile, the cubic Co2MnO4 nanorods present superior stability with negligible degradation of their electrocatalytic activity after a continuous operation time of 10,000 seconds, which is much better than the commercial Pt/C electrocatalvst.

Facile synthesis of magnetic-plasmonic nanocomposites as T1 MRI contrast enhancing and photothermal therapeutic agents

Nanocomposites combining magnetic and plasmonic components have received widespread attention in recent years due to their potential applications in biomedical research. Herein, we describe a facile method for growing small iron oxide nanoparticles on various plasmonic core materials with different shapes and surfaces by utilizing a polypyrrole interlayer. By focusing on Au nanorod@polypyrrole@iron oxide （Au NR@PPy@FexO） nanocomposites, we show that these systems exhibit a low r2/rl ratio of 4.8, making them efficient T1 positive contrast-enhancing agents for magnetic resonance imaging （MRI）. Moreover, we show that the nanocomposites are excellent photothermal agents in the second near infrared region, with high photothermal conversion efficiency, reaching up to 46%. In addition, the Au NR@PPy@FexO nanocomposites show very low cytotoxicity. In summary, the present results highlight the great potential of the synthetic method and the nanocomposites developed in this study for T~ MRI and/or infrared thermal imaging-guided photothermal cancer therapeutic applications.

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.

Real-time in vivo visualization of tumor therapy by a near-infrared-II Ag2S quantum dot-based theranostic nanoplatform

Real-time and objective feedback of therapeutic efficacies would be of great value for tumor treatment. Here, we report a smart Ag2S QD-based theranostic nanoplatform （DOX@PEG-Ag2S） obtained by loading the anti-cancer drug doxorubicin （DOX） into polyethylene glycol-coated silver sulfide quantum dots （PEG-Ag2S QDs） through hydrophobic-hydrophobic interactions, which exhibited high drug loading capability （93 wt.% of DOX to Ag2S QDs）, long circulation in blood （t1/2 = 10.3 h）, and high passive tumor-targeting efficiency （8.9% ID/gram） in living mice where % ID/gram reflects the probe concentration in terms of the percentage of the injected dose （ID） per gram of tissue. After targeting the tumor tissue, DOX from PEG-AgRS cargoes was selectively and rapidly released into cancer cells, giving rise to a significant tumor inhibition. Owing to the deep tissue penetration and high spatio-temporal resolution of Ag2S QDs fluorescence in the second near-infrared window （NIR-II）, the DOX@PEG-Ag2S enabled real-time in vivo reading of the drug targeting process and therapeutic efficacy. We expect that such a novel theranostic nanoplatform, DOX@PEG-Ag2S, with integrated drug delivery, therapy and assessment functionalities, will be highly useful for personalized treatments of tumors.

Green synthesis of NiFe LDH/Ni foam at room temperature for highly efficient electrocatalytic oxygen evolution reaction

Clean energy technologies such as water splitting and fuel cells have been intensively pursued in the last decade for their free pollution. However, there is plenty of fossil energy consumed in the preparation of the catalysts,which results in a heavy pollution. Therefore, it is much desired but challenging to fabricate high-efficiency catalysts without extra energy input. Herein, we used a facile one-pot room-temperature method to synthesize a highly efficient electrocatalyst of nickel iron layered double hydroxide grown on Ni foam(NiFe LDH/NF) for oxygen evolution reaction(OER). The formation of the NiFe LDH follows a dissolutionprecipitation process, in which the acid conditions by hydrolysis of Fe^3+ combined with NO3^- could etch the NF to form Ni^2+. Then, the obtained Ni^2+ was co-precipitated with the hydrolysed Fe^3+ to in situ generate NiFe LDH on the NF. The NiFe LDH/NF exhibits excellent OER performance with a low potential of about 1.411 V vs. reversible hydrogen electrode(RHE) at a current density of 10 m A cm^-2, a small Tafel slope of 42.3 mV dec^-1 and a significantly low potential of ~1.452 V vs. RHE at 100 mA cm^-2 in 1 mol L^-1 KOH. Moreover, the material also keeps its original morphology and structure over 20 h. This energy-efficient strategy to synthesize NiFe LDH is highly promising for widespread application in OER catalyst industry.

Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: long-term survival and functional recovery in canines

Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.

Dual stimuli-activatable versatile nanoplatform for photodynamic therapy and chemotherapy of triple-negative breast cancer

Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to their"always-on"photoactivity in blood circulation.To address this concern,we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors.These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin(TCPP)with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species(RoS)generation.The resultant TCPP derivatives are grafted with a poly(ethylene glycol)(PEG)chain via a matrix metalloproteinase-2(MMP-2)-liable peptide spacer and chelated with Mn^(2+)for magnetic resonance imaging(MRI)capability.The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT.We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin(DOX)and perform fluorescence image-guided combinatorial PDT and chemotherapy,which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model.These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.

All-in-one theranostic nanoplatfbrm with controlled drug release and activated MRI tracking functions for synergistic NIR-II hyperthermiachemotherapyof tumors

Real-time tracking drug release behavior is fundamentally important for avoiding adverse effects or unsuccessful treatment in personalizemedical treatment.However,the development of a non-invasive drug reporting platform still remains challenging.Herein the design of a novelsyn thetic magnetic resonance imaging(MRI)agent for drug release tracking(SMART)is reported,which integrates photothermal core andparamagnetic ion/drug loading shell with a thermal valve in a hybrid structure.Through near-infrared(NIR)-II photothermal effect originatingfrom inner Au-Cu9S5 nanohybrid core,burst release of drugs loaded in the mesoporous silica shell is achieved.The concomitant use of aphase change material not only prevents premature drug release,but also regulates heating effect,keeping local temperature below 45℃,enabling synergistic chemotherapy and mild hyperthermia in vitro and in vivo.Furthermore,the drug release from SMART facilitates protonaccessibility to the paramagnetic ions anchored inside mesopores channels,enhancing Iongitudinal T1 relaxation rate and displaying positivesignal correlation to the amount of released drug,thus allowing norvinvasive real-time monitoring of drug release event.The current studyhighlights the potential of designed MRI nanophores such as SMART for real-time and in-situ monitoring of drug delivery for precisionthera nostic applications.

Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat

Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore important to identify the optimal NSPC type.In our study,we compared the transcriptomes of human fetal brain-derived NSPCs(BNSPCs),spinal cord-derived NSPCs(SCNSPCs)and H9 embryonic stem-cell derived NSPCs(H9-NSPCs)in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo.In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types.In vivo,compared with BNSPCs and H9-NSPCs,SCNSPCs exhibited the best therapeutic effects;in fact,SCNSPCs facilitated electrophysiological and hindlimb functional recovery.This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair,which is of great clinical significance.

A Cascade Targeted and Activatable NIR-ⅡNanoprobe for Highly Sensitive Detection of Acute Myeloid Leukemia in an Orthotopic Model

Acute myeloid leukemia(AML)remains a significant concern in modern medicine.Early diagnosis is the key to improving the therapeutic effects of AML.In the present work,a cascade-targeted and activatable NIR-Ⅱ nanoprobe(Ald&A1094@Ag_(2)S)was developed for early detection of AML in an orthotopic model.Upon intravenous injection,Ald&A1094@Ag_(2)S effectively accumulated in bone tissue due to its high affinity for alendronate(Ald)to the bone.Thereafter,the AML microenvironment allowed for the membrane-penetrating peptide TAT(cell‐penetrating peptide(CGRRRQRRKKRG))to be exposed via pH-sensitive hydrazone bond-mediated detaching of bone-targeted ligands,resulting in efficient internalization of nanoprobes in HL60 cells.Endogenous peroxynitrite(ONOO–)in HL60 cells further activated NIR-Ⅱ fluorescence of Ag_(2)S QDs via A1094 oxidation,thereby inhibiting fluorescence resonance energy transfer(FRET).Such a unique cascade-targeted and activatable strategy enables the nanoprobes to only light up the AML lesion region in the bone marrow with negligible background effects,which holds great potential for clinical applications in the future.

The activity of Zn precursors determines the cation exchange reaction kinetics with Ag_(2)S:Zn-doped Ag_(2)S or Ag_(2)S@ZnS QDs

Cation exchange(CE)has been emerged as a promising post-synthesis strategy of colloidal nanocrystals.However,it is unclear how the cation precursor affects the CE process and the final colloidal nanocrystals.Herein,we utilized two Zn-B Lewis acidbase adduct complexes(B=oleylamine(OAM)and methanol(MeOH))as Zn precursors for CE with Ag_(2)S quantum dots(QDs).Our study revealed that the steric hindrance and complexing capabilities of Zn precursor significantly affect the CE kinetics.As a result,the Zn-doped Ag_(2)S(Zn:Ag_(2)S)and Ag_(2)S@ZnS core–shell QDs were successfully obtained with enormous enhancement of their photoluminescence(PL)intensities.Theoretical simulation showed that the Zn-OAM with higher desolvation energy and spatial hindrance tended to form doped Zn:Ag_(2)S QDs due to the inefficient cation exchange.Whereas the Zn-MeOH with lower exchange barrier promoted the conversion of Ag-S to Zn-S,thus forming Ag_(2)S@ZnS core–shell QDs.We anticipate that this finding will enrich the regulatory approaches of post-synthesis of colloidal nanocrystals with desirable properties.

AgAuSe quantum dots with absolute photoluminescence quantum yield of 87.2%:The effect of capping ligand chain length

Surface ligands of colloidal quantum dots(QDs)have a profound influence on their surface states,which has been verified in the studies of the effect of ligand head groups on the photoluminescence(PL)properties of QDs.However,the investigation of the ligand chain length is limited.Here,we systematically explored the effect of chain length on the Ag_(2)Se QDs by selecting three ligands,1-octanethiol(OTT),1-dodecanethiol(DDT),and 1-hexadecanethiol(HDT),with diverse chain lengths.We found that the PL intensity of Ag_(2)Se QDs increased with the decrease of the ligand chain length due to the enhanced passivation of surface defects emerging from the robust QD-ligand interface binding affinity and the weaker hydrophobic chain–chain interaction.Subsequently,AgAuSe QDs terminated with OTT were obtained by alloying parent OTT-Ag_(2)Se QDs with Au precursor with a record absolute PL quantum yield(PLQY)of 87.2%at 970 nm,facilitating ultrasensitive in vivo angiography imaging in a nude mouse model.We expect that our finding of the important role of the ligand chain length on the optical properties of QDs will be suggestive to the design and synthesis of high-quality QDs,and also look forward to the clinical applications of the ultra-bright AgAuSe QDs.

An intelligent DNA nanodevice for precision thrombus therapy

Obstruction of blood vessels(thrombosis)due to blood clots is one of the main causes of death worldwide and is associated with many cardiovascular diseases,such as myocardial infarction,ischemic stroke,and pulmonary embolism[1].Thrombolytic therapy is currently the preferred treatment for acute thrombosis and is administered intravenously with thrombolytic drugs,such as tissue plasminogen activator(tPA)[2].

Manipulating exciton confinement for stable and efficient flexible quantum dot light-emitting diodes

Flexible quantum dot light-emitting diodes(QLEDs)show great promise for the next generation of flexible,wearable,and artificial intelligence display applications.However,the performance of flexible QLEDs still lags behind that of rigid substrate devices,hindering their commercialization for display applications.Here we report the superior performance of flexible QLEDs based on efficient red ZnCdSe/ZnS/ZnSe QDs(A-QDs)with antitype-I nanostructures.We reveal that using ZnS as an intermediate shell can effectively confine the exciton wavefunction to the inner core,reducing the surface sensitivity of the QDs and maintaining its excellent emission properties.These flexible QLEDs exhibit a peak external quantum efficiency of 23.0%and a long lifetime of 63,050 h,respectively.The anti-type-I nanostructure of A-QDs in the device simultaneously suppresses defectinduced nonradiative recombination and balances carrier injection,achieving the most excellent performance of flexible QLEDs ever reported.This study provides new insights into achieving superior performance in flexible QD-based electroluminescent devices.

Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model

Nerve conduit is one of strategies for spine cord injury(SCI)treatment.Recently,studies showed that biomaterials could guide the neurite growth and promote axon regeneration at the injury site.However,the scaffold by itself was difficult to meet the need of SCI functional recovery.The basic fibroblast growth factor(bFGF)administration significantly promotes functional recovery after organ injuries.Here,using a rat model of T9 hemisected SCI,we aimed at assessing the repair capacity of implantation of collagen scaffold(CS)modified by collagen binding bFGF(CBD-bFGF).The results showed that CS combined with CBD-bFGF treatment improved survival rates after the lateral hemisection SCI.The CS/CBD-bFGF group showed more significant improvements in motor than the simply CS-implanted and untreated control group,when evaluated by the 21-point Basso-Beattie-Bresnahan(BBB)score and footprint analysis.Both hematoxylin and eosin(H&E)and immunohistochemical staining of neurofilament(NF)and glial fibrillary acidic protein(GFAP)demonstrated that fibers were guided to grow through the implants.These findings indicated that administration of CS modified with CBD-bFGF could promote spinal cord regeneration and functional recovery.

MoSe2 porous microspheres comprising monolayer flakes with high electrocatalytic activity

A facile colloidal route to synthesize MoSe2 porous microspheres with diameters of 400-600 nm made up of MoSe2 monolayer flakes （-0.7 nm in thickness） is reported. The solvents trioctylamine （TOA） and oleylamine （OAM） are found to play important roles in the formation of MoSe2 microspheres, whereby TOA determines the three-dimensional （3D） microspherical morphology and OAM directs the formation of MoSes monolayer flakes. The robust 3D MoSe2 microspheres exhibit remarkable activity and durability for the electrocatalytic hydrogen evolution reaction （HER） in acid, maintaining a small onset overpotential of -77 mV and keeping a small overpotential of 100 mV for a current density of 5 mA/cm2 after 1,000 cycles. In addition, similar 3D WSe2 microspheres can also be prepared by using this method. We expect this facile colloidal route could further be expanded to synthesize other porous structures which will find applications in fields such as in energy storage, catalysis, and sensing.

1.82 wt.% Pt/N, P co-doped carbon overwhelms 20 wt.% Pt/C as a high-efficiency electrocatalyst for hydrogen evolution reaction

Cost-effective electrocatalysts for the hydrogen evolution reaction （HER） play a key role in the field of renewable energy. Although tremendous efforts have been devoted to the search of alternative materials, Pt/C is still the most efficient electrocatalyst for the HER. Nevertheless, decreasing the loading of Pt in the designed eletrocatalysts is of significance. However, with low Pt loading, it is challenging to maintain excellent catalytic performance. Herein, a new catalyst （Pt/NPC） was prepared by dispersing Pt nanoparticles （PtNPs） with an average diameter of 1.8 nm over a three-dimensional （3D） carbon network co-doped with N and P. Because of the high electronegativity of the N and P dopants, PtNPs were uniformly dispersed on the carbon network via high electronic affinity between Pt and carbon, affording a Pt/NPC catalyst; Pt/NPC exhibited superior HER activity, attributed to the down-shift of the Pt d-band caused by the donation of charge from N and P to Pt. The results show that Pt/NPC with an ultralow Pt loading of 1.82 wt.% exhibits excellent HER performance, which corresponds to a HER mass activity 20.6-fold greater than that observed for commercial 20% Pt/C at an overpotential of 20 mV vs. RHE.

Atomic-scale Pt clusters decorated on porousα-Ni(OH)_2 nanowires as highly efficient electrocatalyst for hydrogen evolution reaction

The synthesis of atomic-scale metal catalysts is a promising but very challenging project. In this work, we successfully fabricated a hybrid catalyst of PL/Ni（OH）2 with atomic-scale Pt clusters uniformly decorated on porous Ni（OH）2 nanowires （NWs） via a facile room-temperature synthesis strategy. The as-obtained Ptc/Ni（OH）2 catalyst exhibits highly efficient hydrogen evolution reaction （HER） performance under basic conditions. In 0.1moll-1 KOH, the Ptc/Ni（OH）2 has an onset overpotential of -0 mV vs. RHE, and a significantly low overpotential of 32 mV at a current density of 10mAcm-2, lower than that of the com- mercial 20% Pt/C （58 mV）. The mass current density data illustrated that the PL/Ni（OH）2 reached a high current den- sity of 6.34Amg^-1i at an overpotential of 50 mV, which was approximately 28 times higher than that of the commercial Pt/C （0.223Amg^-1i） at the same overpotential, proving the high-efficiency electrocatalytic activity of the as-obtained Ptc/Ni（OH）2 for HER under alkaline conditions.