Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Design and Implementation of Multi-collaborative Training System

With the rapid development of computer technology,network and information technology have been widely used in people’s daily lives,which has brought great convenience to labor and life.At the same time,people are increasingly dependent on computer technology.In this case,the social demand for computer professionals is increasing.However,due to the rapid changes and continuous updates of computer technology,the training of talents in computer specialty in China is far from meeting the demand and quality requirements of the society for this kind of talents.Colleges and universities are the important departments that cultivate computer professionals and technicians for the society.When cultivating talents in computer specialty,colleges and universities must conform to the requirements of the development of the times,adjust teaching strategies in a timely manner according to the actual needs of the society,build a talent training system,build a practical training teaching system of computer specialty,innovate teaching modes and teaching contents,and improve students’professional skills through perfect practical teaching,so as to ensure that they can skillfully apply computer technology to solve practical problems in the learning process and further improve their employment competitiveness.Therefore,this paper analyzes the practical teaching system of computer specialty,puts forward corresponding solutions to the existing problems,constructs a multi-collaborative practical training system,and implements the system.The implementation results show that the system can better meet the needs of students at different levels,and the results are fairer.Students’recognition and sense of acquisition of courses have also been greatly improved.The accumulated experience and data also provide good support for our continuous improvement of the system in the future.

Construction and Implementation of OBE-based Practical Course for Software System Development with Solid Foundation and Continuous Improvement

Software engineering is a highly practical major,and students need a lot of hands-on practice to transform the theoretical contents learned in class into the practical ability to solve practical problems,so practical courses are an essential and important part in the process of training talents in software engineering.From the point of view of cultivating talents in software engineering,this paper expounds the important position of practical courses in software engineering in the process of cultivating talents,analyzes the problems in the existing practical courses,and puts forward the construction ideas and characteristics of practical courses in software engineering which strengthen the foundation,advance steadily,and face the output.Taking the practical course for software system development as an example,this paper introduces in detail the concrete implementation process,achievements,existing problems and countermeasures of the course.

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways.Here,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and dysmyelination.Furthermore,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal transport.Specifically,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and TrkB.DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and homeostasis.This finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

ENHANCED EXPRESSION OF hALP GENE CONFERS CELLULAR RESISTANCE TO H_2O_2 INDUCED SENESCENCE

Objective To investigate the H_ 2O_ 2-induced expression of human histone acetyltransferase-like protein (hALP), a telomerase regulation-associated gene, and its effects on the stress-triggered cellular senescence.Methods The induced expression of hALP was measured by semi-quantitative RT-PCR and immunofluorescent histochemistry after treatment of HeLa cells by H_ 2O_ 2.The effects of hALP expression on cellular responses to H_ 2O_ 2 were analyzed by MTT, flowcytometry, and SA-β-gal staining, respectively.Results hALP mRNA could be dose-dependently induced by treatments of 0.2-1.6 mmol/L H_ 2O_ 2, and the induction could be observed after 6 hours and kept for 36 hours in the presence of 0.4 mmol/L H_ 2O_ 2.Meanwhile, the immunofluorescent staining showed marked stronger nuclear intensity of hALP protein in H_ 2O_ 2-treated HeLa cells.In the treatment of H_ 2O_ 2, the ectopic expression of hALP enhanced continuous growth and overcame G_ 2/M arrest as well as decreased senescence-associated β-gal staining.On the contrary, the transfected clones with antisense or blank vector and original HeLa cells presented growth suppression, G_ 2/M delay and higher percentage of SA-β-gal activities in the presence of H_ 2 O_ 2.Conclusions The expression of hALP could be up-regulated by treatment of H_ 2O_ 2, and elevated expression could enhance cellular resistance to H_ 2O_ 2-induced cellular senescence.The data might be of references to elucidation of basic biological function of hALP gene and its associated telomerase activity.

A self-guidance biological hybrid drug delivery system driven by anaerobes to inhibit the proliferation and metastasis of colon cancer

Colorectal cancer is often accompanied by multiple organ metastasis.Anaerobic Bifidobacterium Infantis(BI)bacterial can selectively grow in hypoxic colorectal tumor microenvironment(TME),to own the natural advantage of preferentially colorectal tumor targeting.Herein,a self-guidance biological hybrid drug delivery system(BI-ES-Fe Alg/DOX)based on BI was constructed to inhibit the proliferation and metastasis of colon cancer.Results demonstrated that BI-ES-Fe Alg/DOX could overcome physical barriers to target and accumulate in colon tumor tissues.Then DOX was released to kill tumor cells along with the phase transition(solid to liquid)of Fe Alg hydrogel,due to Fe3+was reduced to Fe^(2+)by intracellular GSH.Meanwhile,BI-ES selectively colonized into tumors and expressed endostatin(ES)protein to down-regulate VEGF and b FGF expression,exerting anti-angiogenic effect.Moreover,Fe Alg catalyzed H_(2)O_(2)in the local tumor to generate cytotoxic·OH,further enhancing the antitumor effect.The pharmacodynamic result in AOM/DSS model proved that BI-ES-Fe Alg/DOX had the best therapeutic effect,with the final V/V0of 2.19±0.57,which was significantly lower than the other groups.Meanwhile,on CT-26tumor-bearing model,it also showed an outstanding anti-tumor effect with inhibition rate of 82.12%±3.08%.In addition,lung metastases decreased significantly in tumor metastasis model after BI-ES-Fe Alg/DOX treatment.

SPECIFIC UP-REGULATION OF DNA POLYMERASE BY HUMAN PAPILLOMAVIRUS 16

Obje, etive To analyze how the infection of human papillomavirus 16 （ HPV16 ） affects expression of DNA poly- merase β（DNA polB） with the aim of probing the mechanism of over-expression of DNA polB in human cancers. Methods Four fragments of human DNA polB promoter were amplified and constructed into luciferase reporter vec- tor pGL-Basic, generating pGL-BP, pGL-BMH, pGL-BMS, and pGL-BAT constructs respectively, and co-transfected with HPV16 or HPV6 into Hep2 cells. Luciferase activity was assayed 48 hours after transfectiorL Semi-quantitative RT- PCR was used to measure mRNA expression of endogenous DNA polB. Immunohistochemistry and in situ hybridization were used to analyze DNA polB expression and HPV16 or HPV6 infection in 38 cases of cervical lesions respectively. Results With co-transfection of HPV16 and DNA polB promoter-driving reporters into Hep2 cells, pGL-BP re- porter in full-length DNA polB promoter presented markedly elevated luciferase activities （ P 〈 0.05 ）. However, the other three mutant reporters： pGL-BMH, pGL-BMS, and pGL-BAT, generated no reporting activities in the presence of HPV16 （P 〉0.05 ）. On the contrary, all of polB promoter reporters were little stimulated in co-transfection of HPV6 （P 〉0.05 ）. The transfection of HPV16 could enhance the endogenous polB mRNA expression compared with that of HPV6 （3.42 vs. 0.80, P 〈0.05）. The DNA polB expression was found in 8 of 10 HPV16-positive cervical intraepi- thelial neoplasia grade Ⅲ（ CIN Ⅲ） cases, while was only found in 3 of 11 HPV6-positive condyloma accuminatum cases, but was negative in all chronic cervicitis cases. The correlation of DNA polB expression with HPV16 infection in cervical lesions was significant （ P 〈0.05 ）. Conclusions HPV16 is able to specifically stimulate the expression of DNA polB in human epithelial cells through interaction with the core upstream regulatory sequences of DNA polB promoter. Over-expression of DNA polB might be an explanation for the molecular mechanism underlying HPV-related human cancers.

Design and Implementation of a Comprehensive Training Program for Software Engineering Talents’ Practical Ability

In the process of cultivating software engineering professionals,the practical teaching of professional courses is an indispensable link.In order to enable students to understand,consolidate and master theoretical knowledge,improve the ability to solve problems by combining theory with practice,and achieve the goal of combining theoretical knowledge with practice.Adopting the planning of through-type training,complete the teaching work of three practical courses of software system design,software system construction,and software product construction.Through the implementation of the plan,the digitization of teaching resources,the virtualization of real enterprises,the intelligentization of teaching guidance,the visualization of teaching process,and the panorama of learning process are realized.By adopting the teaching methods of taskdriven online practice teaching,artificial intelligence-based teaching training support and teaching process,and result big data evaluation,the students’comprehensive practical ability can be improved finally,and the whole practice teaching reform can provide experience for the follow-up reform.

Chronology, Geochemistry and Geological Significance of Haizi Bimodal Intrusive Bodies in Wuding District, Central Yunnan

The Haizi diabase-granite porphyry composite rock mass is located in the Wuding-Yanjing taphrogenic trough within the Paleoproterozoic Kangdian fault-uplift zone. According to field observations, the diabase is divided into two types: central facies and marginal facies;the granite porphyry directly contacts the central facies of diabase without transitional intermediate rock. In order to disclose its geological and petrological significances, this paper carried out the LA-ICP-MS zircon U-Pb dating and geochemical investigation on both masses of Haizi diabase and granite porphyry. The results showed that the207Pb/206Pb weighted average age of granite porphyry is 1764 ± 18 Ma and diabase 1765 ± 5.4 Ma. The geochemical investigations revealed that the Haizi diabase is a kind of high-potassium alkaline basalt and the granite porphyry a kind of low-potassium rhyolite, both enriched with high field intensity elements and depleted in large-ion lithophile elements;there is obvious component intermittence between the diabase and the granite porphyry, both being bimodal and showing characteristics of continental rift valley magmatite. The?in situ?Hf isotope of dating zircon showed that mantle materials participated in the formation and emplacement of Haizi granite porphyry and crust materials participated in the formation of diabase. This meant that crustal remelting and accretion of new crust occurred in this region in the 1.7 Ga period. It can be therefore inferred that the Haizi bimodal intrusive rock came into being due to the breakup of Kunyang rift valley and rapid ascent of mantle materials in the 1.7 Ga period, which echoed the global Columbia supercontinent breakup and was the first petrological record of that breakup found at the southwest margin of Yangtze platform.

In situ autophagy regulation in synergy with phototherapy for breast cancer treatment

Autophagy is an important factor in reducing the efficacy of tumor phototherapy(including PTT and PDT).Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT.This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy.To achieve this goal,we first synthesized TRANSFERRIN(Tf)biomimetic mineralized nano-tellurium(Tf-Te)as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly.The autophagy inhibitor hydroxychloroquine(HCQ)and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ.After entering breast cancer cells through the“self-guidance system”,Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation,to efficiently induce PTT/PDT effect.Meanwhile,the disulfide bond broke down in response to GSH,and the nanoparticles disintegrated to release Fe2+and HCQ at fixed points.They simultaneously induce lysosomal alkalinization and increased osmotic pressure,effectively inhibit autophagy,and synergistically enhance the therapeutic effect of phototherapy.In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6%on 4T1 tumor-bearing mice.This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

Toeplitz算子的特征值和特征向量

记L^(2)为单位圆周T上的Lebesgue平方可积函数全体.定义Hardy空间H^(2)是L^(2)中的解析多项式所张成的闭子空间.对于复平面中的单位开圆盘D中的任一点z,函数K_(z)(w)=1/(1-zw)是H^(2)中的再生核函数.对任意的f∈H^(2),众所周知T_(f)K_(z)=f(_(z))K_(z),即K_(z)是T_(f)的属于特征值f(z)的特征向量.反过来,若存在z∈D(或对每一个z∈D),使得K_(z)是T_(f)的特征向量,是否必有f∈H∞针对这些问题,本文给出了以再生核K_(z)为特征向量的Toeplitz算子以及有界线性算子的完全刻画,还给出了以所有的f(z)(z∈D)为特征值的Toeplitz算子的部分刻画.

Generating a reporter mouse line marking medium spiny neurons in the developing striatum driven by Arpp21 cis-regulatory elements

The striatum, as the primary input nucleus in the basal ganglion,plays an important role in neural circuits crucial for the control of critical motivation, motor planning and procedural learning(Kreitzer and Malenka, 2008). Most cells in the striatum are GABAergic, including a large population (90%-95%) of medium spiny neurons (MSNs) and a small population of interneurons.

Laser-induced Janus graphene/poly(p-phenylene benzobisoxazole)fabrics with intrinsic flame retardancy as flexible sensors and breathable electrodes for fire-fighting field

Conventional firefighting clothing and fire masks can protect firemen’s safety to a certain extent,whereas cannot perceive environmental hazards and monitor their physical status in real time.Herein,we fabricated two kinds of Janus graphene/poly(pphenylene benzobisoxazole)(PBO)fabrics by laser direct writing approach and evaluated their performance as intelligent firefighting clothes and fire masks.The results showed that the Janus graphene/PBO fabrics were virtually non-combustible and achieved the highest thermal protection time of 18.91 s ever reported in flame,which is due to the intrinsic flame-retardant nature of PBO fibers.The graphene/PBO woven fabrics-based sensor showed good repeatability and stability in human motion monitoring and NO_(2)gas detection.Furthermore,the piezoelectric fire mask was assembled with graphene/PBO nonwoven fabric as electrode layer and polyvinylidene fluoride(PVDF)electrostatic direct writing film as piezoelectric layer.The filtration efficiency of the fire mask reaches 95%for PM_(2.5)and 100%for PM_(3.0),indicating its effective filtration capability for smoke particles in fires.The respiratory resistance of the piezoelectric fire mask(46.8 Pa)was lower than that of commercial masks(49 Pa),showing that it has good wearing comfort.Besides,the piezoelectric fire mask can be sensitive to the speed and intensity of human breathing,which is essential for indirectly reflecting the health of the human body.Consequently,this work provides a facile approach to fabricate next-generation intrinsic flame-retardant smart textiles for smart firefighting.

Erratum to:Laser-induced Janus graphene/poly(p-phenylene benzobisoxazole)fabrics with intrinsic flame retardancy as flexible sensors and breathable electrodes for fire-fighting field

Erratum to Nano Research 2023,16(5):7600-7608 https://doi.org/10.1007/s12274-023-5382-y The name of the third author in original paper was unfortunately misspelled.It should be“Huimin Wang”,instead of“Huiming Wang”.

Oral nano-formulation improves pancreatic islets dysfunction via lymphatic transport for antidiabetic treatment

Type 2 diabetes mellitus(T2DM)therapy is facing the challenges of long-term medication and gradual destruction of pancreatic isletβ-cells.Therefore,it is timely to develop oral prolonged action formulations to improve compliance,while restoringβ-cells survival and function.Herein,we designed a simple nanoparticle with enhanced oral absorption and pancreas accumulation property,which combined apical sodiumdependent bile acid transporter-mediated intestinal uptake and lymphatic transportation.In this system,taurocholic acid(TCA)modified poly(lactic-co-glycolic acid)(PLGA)was employed to achieve pancreas location,hydroxychloroquine(HCQ)was loaded to execute therapeutic efficacy,and 1,2-dilauroyl-sn-glycero-3-phosphocholine(DLPC)was introduced as stabilizer together with synergist(PLGA-TCA/DLPC/HCQ).In vitro and in vivo results have proven that PLGA-TCA/DLPC/HCQ reversed the pancreatic islets damage and dysfunction,thus impeding hyperglycemia progression and restoring systemic glucose homeostasis via only once administration every day.In terms of mechanism PLGA-TCA/DLPC/HCQ ameliorated oxidative stress,remodeled the inflammatory pancreas microenvironment,and activated PI3K/AKT signaling pathway without obvious toxicity.This strategy not only provides an oral delivery platform for increasing absorption and pancreas targetability but also opens a new avenue for thorough T2DM treatment.

The“two-pronged”nanosystem to precisely improve lipid metabolism and inflammatory microenvironment for atherosclerotic plaque stabilization

The rupture of atherosclerosis(AS)vulnerable plaque is the major cause of fatal arterial thrombosis related diseases.The lipid dysbolism and pro-inflammatory microenvironment are considered two main driving factors for plaque rupture.Herein,a“two-pronged”nanosystem LCS-Se/Res was designed to efficiently stabilize AS plaques,by precisely regulating lipid metabolism and inflammatory microenvironment.LCS-Se/Res was constructed with the core of resveratrol(Res)loaded selenium(Se)nanoparticles(NPs),and the shell(LCS)of targeting peptide(LSIPPKA)modified chitosan(CS).This system was stable in blood circulation.When it arrived at the plaque site,LCS-Se/Res could actively recognize the highly expressed lectin-like oxidized low-density lipoprotein receptor 1(LOX-1)receptor and accumulate there.Thereafter,Res was released from LCS-Se nanocarriers in situ by responding to acidic plaque microenvironment.On the one hand,Res increased autophagy flux in damaged endothelial cells by activating cAMP-PKA-AMPK-SIRT1 signaling pathway to promote lipid degradation.Interestingly,LCS-Se also promoted cholesterol efflux to improve lipid metabolism.On the other hand,fixed-point separated Res and LCS-Se synergistically improved plaque inflammatory microenvironment by reversing macrophage phenotype(M1 to M2)and alleviating plaque oxidative stress.Pharmacodynamics result proved that the plaque vulnerability index(VI)decreased from 1.39±0.282 to 0.108±0.02 after LCS-Se/Res treatment.In short,this study provided a new therapeutic strategy for the atherosclerosis through the two-pronged approach.

Construction of Software Design and Programming Practice Course in Information and Communication Engineering

Innovation and entrepreneurship education is becoming one of the important goals of higher education in China.According to the requirements of the Ministry of Education to deepen the reform of innovation and entrepreneur-ship education in colleges and universities,we propose a core principle of“from basis to comprehensiveness,and then to innovation”to construct the software design and programming practice course in the information and communication engineering discipline.We have integrated specialized knowledge teaching with innovation and entrepreneurship training,implemented a series of experimental projects that integrate theory with practice,and explored mixed teaching methods and diversified examination methods.In this paper,details about software design and programming practice course construction are shown from aspects of teaching content,teaching methods,and examination methods.These course construction experiences will benefit teachers who engage in innovative practical courses in the information and communication engineering discipline.

Ozanimod(RPC1063)在少突胶质前体细胞分化中的作用和机制

目的:研究Ozanimod(RPC1063)在少突胶质前体细胞(oligodendrocyte precursor cell,OPC)分化中的作用,并初步探讨其分子机制。方法:利用免疫吸附法直接分离OPC诱导培养,使用免疫荧光染色、实时荧光定量PCR(quantitative real time-PCR,qRT-PCR)对细胞进行鉴定。qRTPCR法检测大脑皮层发育、OPC分化过程中的S1pr家族基因mRNA水平变化。OPC经不同浓度RPC1063处理后,使用MTT法、ATP细胞活性检测法、免疫荧光染色、qRT-PCR和Western blot检测RPC1063对OPC分化细胞数目、mRNA或蛋白水平的影响。结果:利用免疫吸附法可获得高纯度的OPC;而MTT、ATP检测结果显示在0、0. 1、1、5、50、100nmol/L浓度下,RPC1063对细胞活性无明显影响。进一步研究发现,RPC1063处理OPC后,O4、MBP阳性细胞形态舒展,MBP蛋白表达量增加,OPC分化相关基因Mbp、Mag、Sox10、Cnp的mRNA水平增加。机制上,少突胶质细胞系Oli-neu或OPC经RPC1063处理5min后,AKT-mTOR信号通路相关蛋白p-AKT、p-mTOR、p-4EBP1显著增加,OPC经RPC1063处理48h后,p-AKT、p-mTOR蛋白水平增加;而抑制m TOR活性,RPC1063作用减弱。结论:RPC1063通过AKT-mTOR信号通路促进少突胶质前体细胞的分化。

Fluid Inclusion and H-O Isotope Geochemistry of the Phapon Gold Deposit, NW Laos: Implications for Fluid Source and Ore Genesis

The Phapon gold deposit, located in northern Laos, is a unique large-scale gold deposit in Luang Prabang-Loei metallogenic belt. It is hosted in the Lower Permian limestone and controlled by a NE-trending ductile-brittle fault system. There are three types of primary ore including auriferous calcite vein type, disseminated type, and breccia type, and the first two are important in the Phapon gold deposit. Based on fluid inclusion petrography and microthermometry, three types of primary fluid inclusions including type 1 liquid-rich aqueous, type 2 vapor-rich aqueous and type 3 daughter mineralbearing aqueous were identified in hydrothermal calcite grains. The ore-forming fluids are normally homogeneous, as indicated by the widespread type 1 inclusions with identical composition. The coexistence of type 1 and type 2 inclusions, showing similar final homogenization temperature but different compositions, indicate that fluid immiscibility did locally take place in both two types of ores. The results of microthermometry and H-O isotopes geochemistry indicate that there are little differences on ore-fluid geochemistry between the auriferous calcite vein-type and disseminated type ores. The oreforming fluids are characterized by medium-low temperatures(157–268 oC) and low salinity(1.6 wt.%–9.9 wt.% NaCl eq.). It is likely to have a metamorphic-dominant mixed source, which could be associated with dehydration and decarbonisation of Lower Permian limestone and Middle–Upper Triassic sandstones during the dynamic metamorphism. The fluid-wallrock interaction played a major role, and the locally occurred fluid-immiscible processes played a subordinate role in gold precipitation. Combined with the regional and ore deposit geology, and ore-fluid geochemistry, we suggest that the Phapon gold deposit is best considered to be a member of the epizonal orogenic deposit class.

In situ triggering antitumor efficacy of alcoholabuse drug disulfiram through Cu-based metalorganic framework nanoparticles

Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in cancer treatment.Herein,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanoparticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility.Notably,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu;leakage in blood circulation,thus showing excellent biosafety.Once accumulating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu;simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment.This profile lead to in situ chelation reaction between DSF and Cu;,generating toxic DSF/Cu complex against tumor cells.Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of DSF.This system provided a promising strategy for the application of DSF in tumor therapy.