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1.
Chem Commun (Camb) ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396929

RESUMO

A dual-functional peptide-PNA (peptide nucleic acid) conjugate consisting of a PNA G3-tract and an RHAU23 peptide is devised to target nucleic acids bearing three tandem guanine tracts (G-tracts). The PNA G3-tract joins the three G-tracts to form a stable bimolecular G-quadruplex (G4) and the resulting G4 is then bound by the RHAU23 moiety to form an extra stable G4-peptide complex. Owing to this synergistic dual structural enforcement, the conjugate accomplished extremely high selectivity and nM to sub-nM affinities towards its targets that are up to 1000 times greater than the small molecule G4 ligands. As a result, the conjugate impacts the tracking activity of motor proteins on DNA with superior selectivity and potency that are rarely seen in other G4-targeting approaches.

3.
J Biophotonics ; : e202000046, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32359023

RESUMO

Bulk motion seriously degrades the image quality of optical coherence tomography angiography (OCTA). Conventional correction methods focus on in-plane displacement, while the bulk motion component perpendicular to B-scans also introduces noise. This work first presents an evaluation of this component using a specific scan protocol and an approximate expression derived from peak-normalized cross-correlation values, and then quantitatively assesses how interplane bulk motion noise reduce the sensitivity of cross-sectional angiograms. Finally, we developed a repetitive bulk motion correction method based on the estimated displacements and redundant volume scans. The correction does not require registration and angiogram reconstruction of low flow sensitivity frames, and the results of in vivo mice skin OCTA imaging experiments show that the proposed method can effectively reduce bulk motion noise caused by cardiac and respiratory motion and occasional shaking, and improve OCTA image quality, which has practical significance for clinical OCTA diagnosis and analysis.

4.
Lupus ; : 961203320922301, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356674

RESUMO

INTRODUCTION: The present study aimed to investigate the prevalence and influential factors of thrombocytopaenia in systemic lupus erythematosus (SLE) patients among the Chinese population in order to provide evidence for improving the treatment and nursing of SLE patients. METHODS: A retrospective analysis of 3140 SLE patients admitted to two large tertiary hospitals was conducted in Anhui, China, from 2011 to 2018. In addition, the influential factors related to SLE with thrombocytopaenia were analysed through univariate and multivariate analysis. RESULTS: A total of 804 SLE patients had thrombocytopaenia (25.6%). The top 5 clinical manifestations of SLE inpatients were proteinuria (51.0%), lupus nephritis (45.9%), new rash (38.4%), haematuria (36.7%) and pyuria (32.2%). The incidence of neurological manifestations, oral mucosal ulceration, pleurisy, pericarditis, hyperglycaemia, leucocytopaenia, urinary casts, haematuria, pyuria and high disease activity in the thrombocytopaenia group were higher than those in the non-thrombocytopaenia group (p < 0.05). Multivariate analysis showed age (odds ratio (OR) = 1.009, p = 0.005), neurological manifestations (OR = 1.373, p = 0.048), pericarditis (OR = 1.394, p = 0.048), hyperglycaemia (OR = 1.717, p < 0.001), leucocytopaenia (OR = 2.551, p < 0.001), haematuria (OR = 1.582, p < 0.001), serum C3 level <0.85 g/L (OR = 1.525, p = 0.001), serum C4 concentration <0.10 g/L (OR = 1.287, p = 0.020), serum CRP concentration <8 ng/L (OR = 1.314, p = 0.005), prothrombin time >15.30 seconds (OR = 1.479, p = 0.032), activated partial thromboplatin time >45 seconds (OR = 1.924, p < 0.001) and thrombin time >21 seconds (OR = 1.629, p = 0.015) were associated with thrombocytopaenia. CONCLUSION: Thrombocytopaenia has a high prevalence in SLE patients and is related to some baseline, clinical and laboratory characteristics, affecting multiple organs and systems.

5.
Mol Oncol ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32364663

RESUMO

Long noncoding RNAs (lncRNAs) have emerged as crucial regulators for a myriad of biological processes, and perturbations in their cellular expression levels have often been associated with cancer pathogenesis. In this study, we identified AATBC (apoptosis associated transcript in bladder cancer, LOC284837) as a novel lncRNA. AATBC was found to be highly expressed in nasopharyngeal carcinoma (NPC), and increased AATBC expression was associated with poor survival in patients with NPC. Furthermore, AATBC promoted migration and invasion of NPC cells in vitro, as well as metastasis in vivo. AATBC upregulated the expression of the desmosome-associated protein Pinin (PNN) through miR-1237-3p sponging. In turn, PNN interacted with the epithelial-mesenchymal transition (EMT) activator ZEB1, and upregulated ZEB1 expression to promote EMT in NPC cells. Collectively, our results indicate that AATBC promotes NPC progression through the miR-1237-3p-PNN-ZEB1 axis. Our findings indicate AATBC as a potential prognostic biomarker or therapeutic target in NPC.

6.
Taiwan J Obstet Gynecol ; 59(3): 451-455, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32416898

RESUMO

OBJECTIVE: The L1 cell adhesion molecule (L1CAM) gene, encodes the L1 cell adhesion molecule, is involved in the central nervous system development. Its mutations result in L1 syndrome which is associated with brain malformation and nervous developmental delay. CASE REPORT: We presented three fetuses with hydrocephalus and agenesis of the corpus callosum detected by ultrasound, followed by medical exome sequencing (MES) test with L1CAM mutations: two known missense mutation c.551G > A (p. R184Q) and c.1354G > A (p. G452R), and a novel frameshift mutation c.1322delG which causes the early termination of translation (p. G441Afs∗72). By utilizing multiple computational analysis, all the variants were scored to be likely pathogenic. CONCLUSION: Combined use of ultrasound and MES to identify the molecular etiology of fetal anomalies may contribute to expanding our knowledge of the clinical phenotype of L1 syndrome observed in the south Chinese population.

7.
Adv Mater ; : e2001740, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32390225

RESUMO

The low Coulombic efficiency of the lithium metal anode is recognized as the real bottleneck to practical high-efficiency lithium metal batteries with limited Li excess. The grain size and microstructure of deposited lithium strongly influences the lithium plating/stripping efficiency. Here, a solubilizer-mediated carbonate electrolyte that can realize grain coarsening of lithium deposits (>20 µm in width) with oriented columnar morphology, which is in sharp contrast with conventional nanoscale dendrite-like lithium deposits in carbonate electrolytes, is reported. It exhibits improved Li Coulombic efficiency to 98.14% at a high capacity of 3 mAh cm-2 over 150 cycles, because the colossal lithium deposition with minimal tortuosity can maintain the bulk Li with continuous electron conducting pathway during the stripping process, thus enabling efficient Li utilization. Li/NMC811 full batteries, composed of thin Li anode (45 µm) and a high-capacity NMC811 cathode (16.7 mg cm-2 ), can achieve at least 12 times longer lifespan (200 cycles).

8.
Artigo em Inglês | MEDLINE | ID: mdl-32410377

RESUMO

Rechargeable Li metal anode coupling with high-voltage cathodes is a promising tendency for high-energy-density batteries exceeding 300 Wh kg-1. However, achieving long lifespan under realistic conditions remains a "Gordian knot" for practical-used cells because of the low Li reversibility and electrolyte exhaustion. Here, we report an advancing dual-additives electrolyte containing unique solvation structure of tris(pentafluorophenyl)borane additives and lithium nitrate (LiNO3) in carbonate-based electrolyte, which can generate the outer-Li2O robust solid electrolyte interface and F-,B-containing conformal cathode electrolyte interphase. The resulting stable ion transport kinetics enables excellent cycling of Li/LiNi0.8Mn0.1Co0.1O2 for 140 cycles with 80% capacity retention under highly challenging conditions (~295.1 Wh kg-1 at cell-level). The electrolyte also exhibits high cycling stability for 4.6 V LiCoO2 (160 cycles with 89.8% capacity retention) and 4.95V LiNi0.5Mn1.5O4 cathode.

9.
Cell Chem Biol ; 2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32359427

RESUMO

α-Synuclein (α-syn) overload is strongly associated with Parkinson disease (PD), and reduction of the α-syn level by targeting the peptide-based system through the autophagy-lysosomal pathway (ALP) is a promising strategy to delay PD progression. However, if the ALP is comprised, targeting the peptide-based proteasomal degradation system would be a good alternative. In this study, we designed a fusion peptide containing an α-syn-binding domain and a short strong proteasome-targeting motif. Our results reveal that this peptide could specifically bind to α-syn, and direct it to the proteasomes for degradation in a recombinant expression system. Furthermore, by adding a membrane-penetrating motif to this fusion peptide, we demonstrated that it could penetrate into cells and consequently suppress the cellular α-syn level through proteasome degradation in a dose- and time-dependent manner. Functionally, these effects rescued the mitochondrial dysfunction and cellular defects caused by α-syn overexpression in the cultured cells and primary neurons.

10.
CNS Neurosci Ther ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32329577

RESUMO

AIMS: Failure of neural tube closure resulting from excessive apoptosis leads to neural tube defects (NTDs). NADPH oxidase 4 (NOX4) is a critical mediator of cell growth and death, yet its role in NTDs has never been characterized. NOX4 is a potential target of miR-322, and we have previously demonstrated that miR-322 was involved in high glucose-induced NTDs. In this study, we investigated the effect of NOX4 on the embryonic neuroepithelium in NTDs and reveal a new regulatory mechanism for miR-322 that disrupts neurulation by ameliorating cell apoptosis. METHODS: All-trans-retinoic acid (ATRA)-induced mouse model was utilized to study NTDs. RNA pull-down and dual-luciferase reporter assays were used to confirm the interaction between NOX4 and miR-322. In mouse neural stem cells and whole-embryo culture, Western blot and TUNEL were carried out to investigate the effects of miR-322 and NOX4 on neuroepithelium apoptosis in NTD formation. RESULTS: NOX4, as a novel target of miR-322, was upregulated in ATRA-induced mouse model of NTDs. In mouse neural stem cells, the expression of NOX4 was inhibited by miR-322; still further, NOX4-triggered apoptosis was also suppressed by miR-322. Moreover, in whole-embryo culture, injection of the miR-322 mimic into the amniotic cavity attenuated cell apoptosis in NTD formation by silencing NOX4. CONCLUSION: miR-322/NOX4 plays a crucial role in apoptosis-induced NTD formation, which may provide a new understanding of the mechanism of embryonic NTDs and a basis for potential therapeutic target against NTDs.

11.
PLoS One ; 15(4): e0230934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32240220

RESUMO

BACKGROUND: There are still limited studies comprehensively examining the diagnostic performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in contrast-induced nephropathy (CIN). The study aimed to investigate and compare the predictive value of NGAL and cystatin C in the early diagnosis of CIN. METHODS AND MATERIALS: We searched the PubMed, EMBASE and Cochrane Library databases until November 10, 2019. The methodological quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling were performed to summarize and compare the diagnostic performance of blood/urine NGAL and serum cystatin C in CIN. Subgroup and meta-regression analyses were performed according to the study and patient characteristics. RESULTS: Thirty-seven studies from thirty-one original studies were included (blood NGAL, 1840 patients in 9 studies; urine NGAL, 1701 patients in 10 studies; serum cystatin C, 5509 patients in 18 studies). Overall, serum cystatin C performed better than serum/urine NGAL (pooled DOR: 43 (95%CI: 12-152); AUROC: 0.93; λ: 3.79); serum and urine NGAL had a similar diagnostic performance (pooled DOR: 25 (95%CI: 6-108)/22(95%CI: 8-64); AUROC: 0.90/0.89; λ: 3.20/3.08). Meta-regression analysis indicated that the sources of heterogeneity might be CIN definition, assays, and nationalities. CONCLUSION: Both NGAL and cystatin C can serve as early diagnostic indicators of CIN, while cystatin C may perform better than NGAL.

12.
J Viral Hepat ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243022

RESUMO

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy-four untreated HBV/HCV co-infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV-active/HCV-active (BACA), HBV-inactive/HCV-active (BICA), HBV-active/HCV-inactive (BACI) and HBV-inactive/HCV-inactive (BICI). Treg frequency was calculated as the fraction of CD4+ Foxp3+ T cells among CD4+ T cells. Treg-mediated inhibition was measured as percent of inhibition of T-cell proliferation. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF)-α and interleukin (IL)-10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4+ Foxp3+ T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis-4 (FIB-4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN-γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co-infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.

13.
Nano Lett ; 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32271023

RESUMO

Nanoblisters have attracted attention due to their ability to controllably modulate the properties of two-dimensional materials. The accurate measurement or estimation of their properties is nontrivial and largely based on Hencky's theory. However, these estimates require a priori knowledge of material properties and propagate large errors. Here we show, through a systematic atomic force microscopy study, several strategies that lead to vastly enhanced characterization of nanoblisters. First, we find that nanoblisters may contain both liquid and gas, resolving an ongoing debate in the literature. Second, we demonstrate how to definitively determine the membrane thickness of a nanoblister and show that Hencky's theory can only reliably predict membrane thicknesses for small aspect ratios and small membrane thicknesses. Third, we develop a novel technique to measure the internal pressures of nanoblisters, which quantitatively agrees with Hencky's theory but carries a 1 order smaller propagated error.

14.
J BUON ; 25(1): 262-267, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277640

RESUMO

PURPOSE: Drug resistance in lung cancer is a growing and challenging problem affecting the overall treatment and quality of the patient's life. The main purpose of the current study was to investigate the anticancer effects of flavokawain-B in gemcitabine-resistant non-small lung cancer cells (NSCLC) along with evaluating its mode of action by studying its effects on programmed cell death, ROS production, cell migration and invasion and PI3K/AKT signalling pathway. METHODS: Cell proliferation rate was studied using MTS cell viability assay while apoptosis induction by flavokawain-B was studied by fluorescence microscopy using DAPI staining as well as flow cytometry using Annexin V-FITC/propidium iodide (PI). Effects on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were studied by flow cytometry using Rh-123 and DCH-DA dyes respectively. Effects on cell migration and cell invasion were examined by in vitro wound healing assay and transwell assay respectively. Changes in PI3K/AKT protein expressions were evaluated by western blot. RESULTS: Flavokawain-B selectively inhibited the viability of the human NSCLC cell line A549, indicating lower toxicity compared with normal lung cancer (NLC) CCL-151 cells and both showed dose-dependent inhibition. DAPI and annexin V-FITC/PI staining showed that flavokawain-B led to a dose-dependent onset of apoptosis in lung cancer cells characterized by shrunken cells, fragmented nuclei and chromatin condensation. Western blot showed that flavokawain-B resulted in downregulation of Bcl-2 and upregulation of Bax in a dose dependent manner. Flavokawain-B treatment led to increase of intracellular ROS concentration and decrease of mitochondrial membrane potential (MMP) both showing dose-dependence. It also led to suppression of cell migration and invasion along with blocking PI3K/AKT signalling pathway. CONCLUSIONS: Flavokawain-B targets gemcitabine-resistant NSCLC cells selectively without inducing any significant toxicity in normal cells and these effects are mediated via apoptosis induction, ROS production, loss of MMP, suppression of cell migration and invasion and blocking PI3K/AKT signalling pathway.

15.
Endocrine ; 2020 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-32279225

RESUMO

PURPOSE: To explore the relationship of phenotype and genotype of neonatal diabetes mellitus (NDM) in southwestern China. METHODS: Sixteen cases of NDM admitted to Children's Hospital of Chongqing Medical University from May 2009 to May 2019 were included in this study. The clinical features of the included infants were retrospectively analyzed. Peripheral blood samples of the patients and their parents were collected for mutation detection. RESULTS: Among the 16 cases of NDM, 8 cases were permanent neonatal diabetes mellitus (PNDM) (including 3 clinical syndromes), and 3 cases were transient neonatal diabetes mellitus (TNDM). Mutation detection was performed in six cases. The mutation genes and their loci were FOXP3 p.V408M, KCNJ11 p.C166Y, ABCC8 p.S830P, KCNJ11 p.I182T, KCNJ11 p.G334D, and ZFP57 p.R125X,412. ABCC8 p.S830P was the new found pathogenic site of gene mutation. According to the clinical features and follow-up results, one case was diagnosed as IPEX syndrome, two as DEND syndrome, two as simple PNDM, and one as TNDM. All the TNDM could spontaneously alleviate and then insulin was withdrawn. In PNDM, 75% of those with KATP channel gene mutation could be completely or partially converted to oral sulfonylureas treatment, however, the rest cases needed lifelong insulin replacement therapy. CONCLUSION: The clinical manifestations and treatment regimens of patients with NDM vary according to the type of gene mutation. Even the same mutant genotype has differences in phenotype and response to treatment.

16.
J Mech Behav Biomed Mater ; 105: 103636, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32279855

RESUMO

Mechanical loading plays an important role in maintaining disc health and function, and in particular, excessive mechanical loading has been identified as one of major reasons of disc degeneration. Intervertebral disc organ culture serves as a valuable tool to study disc biology/pathology. In this study, we report the development and validation of a new mouse disc organ culture system by dynamically applying compression loading in a customized micro-culture device tailored for mouse lumbar discs. Precise axial compression force was delivered by a computer-controlled system consisting of a robust micromechanical linear actuator, a force sensitive resistor, and a precision micro-stepping machinery. Customized PDMS-based loading chambers allowed simultaneous loading of six discs per regimen, which streamlined the workflow to reach sufficient statistic power. The detrimental loading regimen of mouse lumbar discs (0.5 MPa of axial compression at 1Hz for 7 days) was demonstrated through live-dead assay, histology, and fluorescence probe based collagen staining. In addition, various mechanical compression profiles were simulated using different materials and geometry designs, potentiating for more sophisticated loading protocols. In summary, we developed a new mechanical loading system for dynamic axial compression of mouse discs, which created a unique avenue to study disc pathogenesis with enriched mouse species-related resources, and complemented the existing spectrum of bioreactor systems predominately for discs of human and large animals.

17.
Int J Oncol ; 57(1): 122-138, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32319600

RESUMO

SAC3 domain containing 1 (SAC3D1) has been reported to be involved in numerous types of cancer. However, the role of SAC3D1 in GC has not yet been elucidated. In the present study, the mRNA expression level of SAC3D1 between GC and normal tissues were assessed with a continuous variable meta­analysis based on multiple datasets from public databases. The protein expression level of SAC3D1 in GC and normal tissues was assessed by an in­house immunohistochemistry (IHC). The association between SAC3D1 expression and some clinical parameters was assessed based on the TCGA and IHC data. Survival analysis was performed to assess the association between SAC3D1 expression and the survival of GC patients. The co­expressed genes of SAC3D1 were determined by integrating three online tools, and the enrichment analyses were performed to determine SAC3D1­related pathways and hub co­expressed genes. SAC3D1 was significantly upregulated in GC tumor tissues in comparison to normal tissues with the SMD being 0.45 (0.12, 0.79). The IHC results also indicated that SAC3D1 protein expression in GC tissues was markedly higher than in normal tissues. The SMD following the addition of the IHC data was 0.59 (0.11, 1.07). The protein levels of SAC3D1 were positively associated with the histological grade, T stage and N stage of GC (P<0.001). The TCGA data also revealed that the SAC3D1 mRNA level was significantly associated with the N stage (P<0.001). Moreover, prognosis analysis indicated that SAC3D1 was closely associated with the prognosis of patients with GC. Moreover, 410 co­expressed genes of SAC3D1 were determined, and these genes were mainly enriched in the cell cycle. In total, 4 genes (CDK1, CCNB1, CCNB2 and CDC20) were considered key co­expressed genes. On the whole, these findings demonstrate that SAC3D1 is highly expressed in GC and may be associated with the progression of GC.

18.
Anal Chem ; 92(9): 6548-6554, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32285660

RESUMO

The signal of the traditional chromogenic systems is directly proportional to analyte concentration, leading to an unsatisfactory sensitivity. Herein, we report a cascade chromogenic system to realize exponential amplification of colorimetric signal through coupling chemical oxidation with photoinduced radical chain reaction. The chemical oxidation of o-phenylenediamine (OPD) by Fe3+ generates Fe2+ and photoactive 2,3-diaminophenazine (DAP). Under blue-light irradiation, DAP initiates the formation of holes and H2O2 that reacts with Fe2+ to hydroxyl radicals (·OH) and Fe3+ via an intersystem crossing (ISC) process. Moreover, the holes oxidize water to yield ·OH as well. The resulting ·OH and regenerated Fe3+ in turn oxidize OPD to yield more DAP, leading to a self-propagating reaction cycle that continues to proceed until all the OPD molecules are consumed, along with a distinct color change from colorless to yellow. Through the generation of the complex between DAP and acetone that limits the ISC process, and therefore quenches the colorimetric signal, the highly sensitive and selective naked-eye detection of acetone is achieved from 50 µM to 3 mM, with a limit of detection of 35 µM. Additionally, the feasibility of this colorimetric assay to detect acetone in real water samples is also demonstrated.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32305941

RESUMO

Learning with streaming data has received extensive attention during the past few years. Existing approaches assume that the feature space is fixed or changes by following explicit regularities, limiting their applicability in real-time applications. For example, in a smart healthcare platform, the feature space of the patient data varies when different medical service providers use nonidentical feature sets to describe the patients' symptoms. To fill the gap, we in this article propose a novel learning paradigm, namely, Generative Learning With Streaming Capricious (GLSC) data, which does not make any assumption on the feature space dynamics. In other words, GLSC handles the data streams with a varying feature space, where each arriving data instance can arbitrarily carry new features and/or stop carrying partial old features. Specifically, GLSC trains a learner on a universal feature space that establishes relationships between old and new features, so that the patterns learned in the old feature space can be used in the new feature space. The universal feature space is constructed by leveraging the relatednesses among features. We propose a generative graphical model to model the construction process, and show that learning from the universal feature space can effectively improve the performance with theoretical guarantees. The experimental results demonstrate that GLSC achieves conspicuous performance on both synthetic and real data sets.

20.
Nanomedicine ; : 102210, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32334102

RESUMO

Intra-articular (IA) drug delivery to treat osteoarthritis (OA) is limited by the short retention time of drugs in the joints due to poor specific targeting and non-responsiveness under acidic environment. A cartilage-targeting peptide was engineered to the surface of ferritin nanocages (CT-Fn) and loaded with an anti-inflammatory drug, metformin (Met), via the self-assembling nature of Fn nanocages. It demonstrated that the CT-Fn/Met could specifically bind to type II collagen, leading to the downregulation of catabolic markers of OA and promotion of cartilage-specific makers in IL-1ß-induced chondrocytes. IA delivery of CT-Fn/Met prolonged the retention time for 3 weeks and remarkably reduced inflammation. Moreover, better release under acidic conditions which enabling longer retention time of Met after IA delivery in OA joints for one more week. CT-Fn/Met could target and efficiently enter chondrocytes, further inducing prolonged IA accumulation and achieving enhanced therapeutic efficacy for OA treatment.

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