查看更多>>摘要：The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors.Here,we present a three-dimensional scaffold,inspired by the physiological process of T-cell proliferation in lymph nodes.This scaffold gathers the function of loading,delivery,activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors.This porous device is made from poly(lactic-co-glycolic acid)by a microfluidic technique with the modification of T-cell stimulatory signals,including anti-CD3,anti-CD28 antibodies,as well as cytokines.This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo.Particularly,it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth.This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.
查看更多>>摘要：Mitochondriopathy inspired adenosine triphosphate(ATP)depletions have been recognized as a powerful way for controlling tumor growth.Nevertheless,selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge.Harnessing the advantages of in vivo self-assembled nanomaterials,we designed an Intracellular ATP Sequestration(IAS)system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like damages.Briefly,the reported transformable nucleopeptide(NLS-FF-T)self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions.By interaction with KPNA2,the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy.As a result,multiple bladder tumor cell lines(T24,EJ and RT-112)revealed that the half-maximal inhibitory concentration(IC50)of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T.Following intravenous administration,NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice.More significantly,this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice.Together,our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages,which provides a potential treatment strategy for malignancies.
查看更多>>摘要：Tissue regeneration is a complicated process that relies on the coordinated effort of the nervous,vascular and immune systems.While the nervous system plays a crucial role in tissue regeneration,current tissue engineering approaches mainly focus on restoring the function of injury-related cells,neglecting the guidance provided by nerves.This has led to unsatisfactory therapeutic outcomes.Herein,we propose a new generation of engineered neural constructs from the perspective of neural induction,which offers a versatile platform for promoting multiple tissue regeneration.Specifically,neural constructs consist of inorganic biomaterials and neural stem cells(NSCs),where the inorganic biomaterials endows NSCs with enhanced biological activities including proliferation and neural differentiation.Through animal experiments,we show the effectiveness of neural constructs in repairing central nervous system injuries with function recovery.More importantly,neural constructs also stimulate osteogenesis,angiogenesis and neuromuscular junction formation,thus promoting the regeneration of bone and skeletal muscle,exhibiting its versatile therapeutic performance.These findings suggest that the inorganic-biomaterial/NSC-based neural platform represents a promising avenue for inducing the regeneration and function recovery of varying tissues and organs.
查看更多>>摘要：Tirapazamine(TPZ)has been approved for multiple clinical trials relying on its excellent anticancer potential.However,as a typical hypoxia-activated prodrug(HAP),TPZ did not exhibit survival advantages in Phase Ⅲ clinical trials when used in combination therapy due to the insufficient hypoxia levels in patients'tumors.In this study,to improve the therapeutic effects of TPZ,we first introduced urea to synthesize a series of urea-containing derivatives of TPZ.All urea-containing TPZ derivatives showed increased hypoxic cytotoxicity(9.51-30.85-fold)compared with TPZ,while maintaining hypoxic selectivity.TPZP,one of these derivatives,showed 20-fold higher cytotoxicity than TPZ while maintaining a similar hypoxic cytotoxicity ratio.To highly efficiently deliver TPZP to the tumors and reduce its side effects on healthy tissues,we further prepared TPZP into a nanodrug with fibrin-targeting ability:FT11-TPZP-NPs.CA4-NPs,a vascular disrupting agent,was used to increase the fibrin level within tumors and exacerbate tumor hypoxia.By being combined with CA4-NPs,FT 11-TPZP-NPs can accumulate in the hypoxia-aggravated tumors and activate sufficiently to kill tumor cells.After a single-dose treatment,FT11-TPZP-NPs+CA4-NPs showed a high inhibition rate of 98.1％against CT26 tumor models with an initial volume of～480 mm3 and four out of six tumors were completely eliminated;it thereby exerted a significant antitumor effect.This study provides a new strategy for improving the therapeutic effect of TPZ and other HAPs in anticancer therapy.
查看更多>>摘要：There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment.We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing.Specifically,pH-responsive H2O2 self-supplying composite nanozyme(MSCO)and pH/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase(PPEL)were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan(CA)and phenylboronic acid-modified oxidized dextran(ODP)to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform.The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites,and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide(NO)release.The composite hydrogel showed'self-diagnostic'treatment for changes in the wound microenvironment.Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage,it promotes wound closure,accelerates wound collagen deposition and angiogenesis,and completely improves the microenvironment of infected wound regeneration,which provides a new method for the design of intelligent wound dressings.
查看更多>>摘要：Organic materials with rich active sites are good candidates of high-capacity anodes in aqueous batteries,but commonly low utilization of active sites limits their capacity.Herein,two isomers,symmetric and asymmetric hexaazatribenzanthraquinone(s-HATBAQand a-HATBAQ),with rich active sites have been synthesized in a controllable manner.It has been revealed for the first time that a sulfuric acid catalyst can facilitate the stereoselective formation of s-HATBAQ Attributed to the reduced steric hindrance in favor of proton insertion as well as the amorphous structure conducive to electrochemical dynamics,s-HATBAQ exhibits 1.5 times larger specific capacity than a-HATBAQ Consequently,the electrode of s-HATBAQwith 50％reduced graphene oxide(s-HATBAQ;50％rGO)delivers a record high specific capacity of 405 mAh g-1 in H2SO4 electrolyte.Moreover,the assembled MnO2//s-HATBAQ;50％rGO aqueous proton full batteries show an exceptional cycling stability at 25℃ and can maintain～92％capacity after 1000 cycles at 0.5 A g-1 at-80℃.This work demonstrates the controllable synthesis of isomers,showcases a wide-temperature-range prototype proton battery and highlights the significance of precise molecular structure modulation in organic energy storage.
查看更多>>摘要：The structural engineering of metastable nanomaterials with abundant defects has attracted much attention in energy-related fields.The high-temperature shock(HTS)technique,as a rapidly developing and advanced synthesis strategy,offers significant potential for the rational design and fabrication of high-quality nanocatalysts in an ultrafast,scalable,controllable and eco-friendly way.In this review,we provide an overview of various metastable micro-and nanomaterials synthesized via HTS,including single metallic and bimetallic nanostructures,high entropy alloys,metal compounds(e.g.metal oxides)and carbon nanomaterials.Note that HTS provides a new research dimension for nanostructures,i.e.kinetic modulation.Furthermore,we summarize the application of HTS—as supporting films for transmission electron microscopy grids—in the structural engineering of 2D materials,which is vital for the direct imaging of metastable materials.Finally,we discuss the potential future applications of high-throughput and liquid-phase HTS strategies for non-equilibrium micro/nano-manufacturing beyond energy-related fields.It is believed that this emerging research field will bring new opportunities to the development of nanoscience and nanotechnology in both fundamental and practical aspects.
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