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1.
Appl Microbiol Biotechnol ; 105(7): 2759-2773, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33683398

RESUMO

The self-assembly of biomacromolecules is an extremely important process. It is potentially useful in the fields of life science and materials science. To carry out the study on the self-assembly of proteins, it is necessary to find out the suitable self-assembly conditions, which have always been a challenging task in practice. Inspired by the screening technique in the field of protein crystallization, we proposed using the same screening technique for seeking suitable protein self-assembly conditions. Based on this consideration, we selected 5 proteins (ß-lactoglobulin, hemoglobin, pepsin, lysozyme, α-chymotrypsinogen (II) A) together with 5 screening kits (IndexTM, BML, Morpheus, JCSG, PEG/Ion ScreenTM) to investigate the performance of these crystallization screening techniques in order to discover new optimized conditions of protein self-assembly. The screens were all kept at 293 K for certain days, and were analyzed using optical microscope, scanning electron microscope, transmission electron microscope, atomic force microscope, fluorescence microscope, and atomic absorption spectroscope. The results demonstrated that the method of protein crystallization screening can be successfully applied in the screening of self-assembly conditions. This method is fast, high throughput, and easily implemented in an automated system, with a low protein consumption feature. These results suggested that such strategy can be applied to finding new conditions or forms in routine research of protein self-assembly. KEY POINTS: • Protein crystallization screening method is successfully applied in the screening of self-assembly conditions. • This screening method can be applied on various kinds of proteins and possess a feature of low protein consumption. • This screening method is fast, high throughput, and easily implemented in an automated system.

2.
Sci Rep ; 11(1): 4494, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627689

RESUMO

Simulated hypobaric hypoxia (SHH) training has been used to enhance running performance. However, no studies have evaluated the effects of a single SHH exposure on healthy mice performance and analyzed the changes of mitochondria-related genes in the central nervous system. The current study used a mouse decompression chamber to simulate mild hypobaric hypoxia at the high altitude of 5000 m or severe hypobaric hypoxia at 8000 m for 16 h (SHH5000 & SHH8000, respectively). Then, the mouse behavioral tests were recorded by a modified Noldus video tracking. Third, the effects of SHH on 8 mitochondria-related genes of Drp1, Mfn1, Mfn2, Opa1, TFAM, SGK1, UCP2 and UCP4, were assessed in cerebellum, hippocampus and gastrocnemius muscles. The results have shown that a single mild or severe HH improves healthy mice performance. In cerebellum, 6 of all 8 detected genes (except Mfn2 and UCP4) did not change after SHH. In hippocampus, all detected genes did not change after SHH. In muscles, 7 of all 8 detected genes (except Opa1) did not change after SHH. The present study has indicated the benefit of a single SHH in healthy mice performance, which would due to the stabilized mitochondria against a mild stress state.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33629455

RESUMO

Silver nanoclusters containing Ag0 atoms protected by amino acids were synthesized and characterized. Chiral superatomic silver nanoclusters [Ag47 L12 (C≡Ct Bu)16 ]BF4 (L=l-/d-valine or l-/d-isoleucine) have been prepared by reducing AgC≡Ct Bu and amino acids (AAs) with NaBH4 . Single crystal X-ray diffraction revealed that these clusters have T symmetry, and the Ag47 metal kernel can be viewed as a tetracapped truncated tetrahedron (Ag17 ) surrounded with six W-shaped Ag5 units. The clusters are homochiral as evidenced by CD measurements. As for the strong CD signals, large contributions are found from the occupied Ag s,p states (superatomic D states) near the Fermi level. Electron counting revealed that these clusters are 18-electron systems, suggesting they are superatomic clusters. The superatomic nature with a 1S2 1P6 1D10 configuration was supported by DFT calculations. This work paves the way of taking AAs as facile chiral induction agents for the synthesis of metal nanoclusters.

4.
Mar Drugs ; 18(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352941

RESUMO

Fungi are a prospective resource of bioactive compounds, but conventional methods of drug discovery are not effective enough to fully explore their metabolic potential. This study aimed to develop an easily attainable method to elicit the metabolic potential of fungi using Aspergillus nidulans laeA as a transcription regulation tool. In this study, functional analysis of Aspergillus nidulans laeA (AnLaeA) and Aspergillus sp. Z5 laeA (Az5LaeA) was done in the fungus Aspergillus sp. Z5. Heterologous AnLaeA-and native Az5LaeA-overexpression exhibited similar phenotypic effects and caused an increase in production of a bioactive compound diorcinol in Aspergillus sp. Z5, which proved the conserved function of this global regulator. In particular, heteroexpression of AnLaeA showed a significant impact on the expression of velvet complex genes, diorcinol synthesis-related genes, and different transcription factors (TFs). Moreover, heteroexpression of AnLaeA influenced the whole genome gene expression of Aspergillus sp. Z5 and triggered the upregulation of many genes. Overall, these findings suggest that heteroexpression of AnLaeA in fungi serves as a simple and easy method to explore their metabolic potential. In relation to this, AnLaeA was overexpressed in the fungus Penicillium sp. LC1-4, which resulted in increased production of quinolactacin A.

6.
Chemosphere ; : 128637, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33097235

RESUMO

BACKGROUND: The adverse effects of TI exposure on pregnant women are still unclear, especially regarding the risk of gestational diabetes mellitus (GDM) Objective: We explored the association between maternal urinary Tl burden and the risk of GDM. METHODS: A subsample of 1789 pregnant women were enrolled who provided spot urine samples before the diagnostic 75-g oral glucose tolerance test. Urinary Tl concentration was measured using inductively coupled plasma mass spectrometry. Logistic regression and covariance analysis were carried out to estimate the association between Tl exposure and GDM risk. RESULTS: The median of urinary Tl concentration was 0.382 µg/L or 0.525 µg/g creatinine (CC-Tl). There were 437 (24.4%) participants who were diagnosed with GDM, and the urinary CC-Tl concentrations of pregnant women with GDM were higher than that of pregnant women without GDM [0.548 (0.402, 0.788) vs 0.518 (0.356, 0.724), p = 0.014]. After adjusting for the relevant covariates, an association between urinary Tl concentrations and GDM was found. In comparison to the pregnant women in the lowest quartile of urinary CC-Tl concentration, the pregnant women in the highest quartile had a higher risk of GDM [OR (95% CI) = 1.44 (1.03, 2.02), p-trend = 0.055]. If limited to the pregnant women without family history of diabetes, the results were still robust [OR (95% CI) = 1.59 (1.11, 2.30), p-trend = 0.012]. CONCLUSION: Urinary CC-Tl concentration was associated with GDM among Chinese pregnant women. Our findings provide evidence that moderately high Tl exposure may be a novel risk factor for pregnant women health.

7.
J Am Chem Soc ; 142(42): 18086-18092, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32985888

RESUMO

Great attention has been paid to nanoclusters having face-centered-cubic (fcc) metal kernels, because of the similarity of metal packing to that of bulk gold. So far, there is no precedent example of an all-alkynyl-protected fcc gold nanocluster with more than 100 gold atoms. We report the synthesis and total structure determination of an alkynyl-protected gold nanocluster [NEt3H]2[Au110(p-CF3C6H4C≡C)48] (Au110). It has an fcc Au86 kernel with 24 peripheral Au(C≡CR)2 staples. The Au86 kernel consists of six close packing layers in the pattern of Au6:Au16:Au21:Au21:Au16:Au6. Electronic absorption spectroscopy shows Au110 has a molecular-like discrete electronic structure, and transient absorption experiments reveal its nonmetallic nature.

8.
Ann Plast Surg ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32881745

RESUMO

BACKGROUND: A plump single eyelid with ptosis is the morphological feature of Asians. Orbicularis oculi muscle (OOM) technique can correct ptosis and get a good appearance. METHODS: A retrospective study was conducted in 121 Chinese patients who underwent double eyelid surgery with medial epicanthoplasty using OOM resection technique from December 2016 to December 2019. Preoperatively, all the patients had good or excellent levator function while skin fold overlapping the upper eyelid margin was found. Palpebral fissure height, upper eyelid margin reflex distance, complications, and cosmetic results were evaluated. Comparisons were performed preoperatively and postoperatively. RESULTS: The study included 121 patients. Mean follow-up time was 12.8 months (range, 6-32 months). Mean margin reflex distance increased from 1.96 ± 0.60 mm preoperatively to 3.74 ± 0.50 mm postoperatively (P < 0.001), mean palpebral fissure height increased from 6.31 ± 0.51 mm preoperatively to 8.33 ± 0.52 mm postoperatively (P < 0.001). Most patients obtained satisfactory results. Only 1 patient was under correction, 2 patients were with mild asymmetry 6 months postoperatively. CONCLUSIONS: Ptosis of the upper eyelid can be corrected by the OOM resection technique without any procedure on levator muscle. This technique can be an alternative method for the correction of ptosis of the upper eyelid.

9.
Am J Transl Res ; 12(7): 3926-3939, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774746

RESUMO

Transient Receptor Potential Melastatin 4 (TRPM4) is a nonselective channel conducting monovalent ions and indirectly regulates intracellular Ca2+. Aberrant expression has been reported in a number of cancers. However, the biological function of TRPM4 in endometrial carcinoma (EC) is still unknown. We find that decreased TRPM4 expression is significantly correlated with a poor prognosis, overall survival (OS, P<0.001) and recurrence-free survival (P=0.002) through The Cancer Genome Atlas (TCGA) datasets in mRNA level. Multivariate Cox regression analysis suggests that TRPM4 is an independent prognostic factor for OS in EC patients. In vitro assays show that TRPM4-deletion results in significant promotion of proliferation and migration in EC cells. We then conducted a gene set enrichment analysis (GSEA) and according to the results, the expression of TRPM4 is modulated by estrogen, which is inhibited by ER antagonist. Furthermore, the silencing of TRPM4 causes a decreased p53 and hyper-activation of EMT, PI3K/AKT/mTOR signaling pathway in EC, as demonstrated in vitro. Overall, these results indicate that TRPM4 is clinically useful in predicting EC prognosis and represent a potential candidate as a new therapeutic target.

10.
Acta Pharmacol Sin ; 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796956

RESUMO

Grincamycins (GCNs) are a class of angucycline glycosides isolated from actinomycete Streptomyces strains that have potent antitumor activities, but their antitumor mechanisms remain unknown. In this study, we tried to identify the cellular target of grincamycin B (GCN B), one of most dominant and active secondary metabolites, using a combined strategy. We showed that GCN B-selective-induced apoptosis of human acute promyelocytic leukemia (APL) cell line NB4 through increase of ER stress and intracellular reactive oxygen species (ROS) accumulation. Using a strategy of combining phenotype, transcriptomics and protein microarray approaches, we identified that isocitrate dehydrogenase 1(IDH1) was the putative target of GCN B, and confirmed that GCNs were a subset of selective inhibitors targeting both wild-type and mutant IDH1 in vitro. It is well-known that IDH1 converts isocitrate to 2-oxoglutarate (2-OG), maintaining intracellular 2-OG homeostasis. IDH1 and its mutant as the target of GCN B were validated in NB4 cells and zebrafish model. Knockdown of IDH1 in NB4 cells caused the similar phenotype as GCN B treatment, and supplementation of N-acetylcysteine partially rescued the apoptosis caused by IDH1 interference in NB4 cells. In zebrafish model, GCN B effectively restored myeloid abnormality caused by overexpression of mutant IDH1(R132C). Taken together, we demonstrate that IDH1 is one of the antitumor targets of GCNs, suggesting wild-type IDH1 may be a potential target for hematological malignancies intervention in the future.

11.
Aging (Albany NY) ; 12(14): 14418-14433, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694237

RESUMO

Whether serine protease inhibitor Kazal type 1 (SPINK1) being associated with enzalutamide (Enz) resistance and metastasis of castration-resistant prostate cancer (CRPC) has not been clear. SPINK1 promoted Enz resistance by upregulating Androgen receptor splicing variant 7 (ARv7), and enhanced the invasion/migration of Enz-resistant cells via ERK/p38/ MMP9 signaling. Furthermore, miR-5089-5p suppressed SPINK1 mRNA through direct binding to its 3'UTR, and reversed its pro-proliferative and pro-metastatic effects. Mice bearing SPINK1-knockdown Enz-resistant PCa tumors showed significantly longer survival compared with those bearing wild-type tumors, while treatment with miR-5089-5p inhibitor abrogated the protective effects of SPINK1 knockdown. Taken together, SPINK1 can be used as a biomarker of resistance to Enz, and the miR-5089-5p/SPINK1/MAPK/MMP9 axis is a suitable therapeutic target against Enz-resistant and metastatic CRPC.Methods: The expression of SPINK1 in Enz-resistant prostate cancer (PCa) cell lines was detected through next-generation sequencing data and metastatic PCa patients. In vivo and in vitro experiments were performed to investigate the role of SPINK1 in Enz-resistance and metastasis.

12.
J Exp Clin Cancer Res ; 39(1): 139, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690100

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (hereinafter referred to as MK5-AS1) in colorectal cancer (CRC) remain mostly unknown. METHODS: In this study, quantitative real-time PCR (qPCR) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 (CCK8), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation (RIP), dual luciferase reporter assay, chromatin immunoprecipitation (ChIP) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model. RESULTS: We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis-regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter. CONCLUSIONS: MK5-AS1 cis-regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.

13.
Mol Brain ; 13(1): 90, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522292

RESUMO

OBJECTIVES: Drp1 is widely expressed in the mouse central nervous system and plays a role in inducing the mitochondrial fission process. Many diseases are associated with Drp1 and mitochondria. However, since the exact distribution of Drp1 has not been specifically observed, it is difficult to determine the impact of anti-Drp1 molecules on the human body. Clarifying the specific Drp1 distribution could be a good approach to targeted treatment or prognosis. METHODS: We visualized the distribution of Drp1 in different brain regions and explicated the relationship between Drp1 and mitochondria. GAD67-GFP knock-in mice were utilized to detect the expression patterns of Drp1 in GABAergic neurons. We also further analyzed Drp1 expression in human malignant glioma tissue. RESULTS: Drp1 was widely but heterogeneously distributed in the central nervous system. Further observation indicated that Drp1 was highly and heterogeneously expressed in inhibitory neurons. Under transmission electron microscopy, the distribution of Drp1 was higher in dendrites than other areas in neurons, and only a small amount of Drp1 was localized in mitochondria. In human malignant glioma, the fluorescence intensity of Drp1 increased from grade I-III, while grade IV showed a declining trend. CONCLUSION: In this study, we observed a wide heterogeneous distribution of Drp1 in the central nervous system, which might be related to the occurrence and development of neurologic disease. We hope that the relationship between Drp1 and mitochondria may will to therapeutic guidance in the clinic.

14.
ACS Chem Biol ; 15(6): 1455-1463, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32378871

RESUMO

As one of the most favorable stimuli, photoactivation provides an advantageous way to manipulate biological objects. In the current study, we have successfully demonstrated the use of light activation guide RNA (gRNA) strategy for controlling CRISPR systems. By conjugating photolabile protecting groups, the CRISPR functions became minimal, but exposure of acylated gRNAs to 365 nm light triggers the removal of masking groups, leading to the rescue of CRISPR functions. Furthermore, our strategy has been successfully used to control gene editing in human cells. This proof-of-concept study therefore demonstrates the promising potential of our strategy to versatile applications in chemical biology.

15.
Opt Express ; 28(8): 11144-11155, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32403631

RESUMO

Nonlinear optical effects in integrated microcavities have been studied extensively with the advantages of strong light-matter interaction, great scalability, and stability due to the small mode volume. However, the pump lasers stimulating nonlinear effects impose obstacles for practical applications, since the material absorption causes thermal resonance drift and instability. Here we experimentally demonstrate an all-optical control of the thermal behavior in optical microcavities for tunable doubly-resonant second-harmonic (SH) generation on an integrated photonic chip. Through an auxiliary control laser, the temperature of a selected microring can be efficiently changed, thus allowing precise frequency tuning of the doubly-resonant wavelength while eliminating the distortion of the lineshape induced by the thermo-optic effect. Although the phase-matching conditions will limit the tuning range of 55GHz, the technique is still potential to achieve a larger tuning range in combination with temperature regulation. Additionally, this approach has the advantage of quick reconfiguration, showing a fast modulation rate up to about 256 kHz. The theoretical model behind our experimental scheme is universal and applicable to other microcavity-enhanced nonlinear optical processes, and our work paves the way for controlling and utilizing the thermal effect in the applications of microcavities.

16.
Angew Chem Int Ed Engl ; 59(28): 11510-11515, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32233052

RESUMO

Developing highly efficient and low-cost photocatalysts for overall water splitting has long been a pursuit for converting solar power into clean hydrogen energy. Herein, we demonstrate that a nonstoichiometric nickel-cobalt double hydroxide can achieve overall water splitting by itself upon solar light irradiation, avoiding the consumption of noble-metal co-catalysts. We employed an intensive laser to ablate a NiCo alloy target immersed in alkaline solution, and produced so-called L-NiCo nanosheets with a nonstoichiometric composition and O2- /Co3+ ions exposed on the surface. The nonstoichiometric composition broadens the band gap, while O2- and Co3+ ions boost hydrogen and oxygen evolution, respectively. As such, the photocatalyst achieves a H2 evolution rate of 1.7 µmol h-1 under AM 1.5G sunlight irradiation and an apparent quantum yield (AQE) of 1.38 % at 380 nm.

17.
J Dairy Sci ; 103(6): 4895-4906, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32229112

RESUMO

The objective of this study was to evaluate the protection conferred by lactoferrin, α-lactalbumin, and ß-lactoglobulin in cerebral ischemia reperfusion (I/R) injury. Rat pheochromocytoma (PC12) cells were used to construct an oxygen and glucose deprivation model in vitro, and ICR mice underwent carotid artery "ligation-relaxation" to construct a cerebral I/R injury model in vivo. The levels of toll-like receptor 4 (TLR4) and downstream factors including nuclear factor-κB, tumor necrosis factor-α, and IL-1ß were measured. Metabonomics detection and data mining were conducted to identify the specific metabolic sponsor of the 3 proteins. The results showed that lactoferrin, α-lactalbumin, and ß-lactoglobulin protected neurons from cerebral I/R injury by increasing the level of bopindolol and subsequently inhibiting the TLR4-related pathway to different degrees; ß-lactoglobulin had the strongest activity of the 3 proteins. In summary, this study is the first to investigate and compare the protective effects of lactoferrin, α-lactalbumin, and ß-lactoglobulin in a cerebral stroke model. The results implicate TLR4 as a novel target of the 3 bioactive proteins to prevent cerebral I/R injury.


Assuntos
Lactalbumina/uso terapêutico , Lactoferrina/uso terapêutico , Lactoglobulinas/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Animais , Glucose/metabolismo , Interleucina-1beta/metabolismo , Lactalbumina/metabolismo , Lactoferrina/metabolismo , Lactoglobulinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Oxigênio/metabolismo , Células PC12 , Ratos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Nat Plants ; 6(4): 360-367, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32231254

RESUMO

Temperature-sensitive genic male sterility (TGMS) lines are widely used in the breeding of hybrid crops1,2, but by what means temperature as a general environmental factor reverses the fertility of different TGMS lines remains unknown. Here, we identified an Arabidopsis TGMS line named reversible male sterile (rvms) that is fertile at low temperature (17 °C) and encodes a GDSL lipase. Cytological observations and statistical analysis showed that low temperature slows pollen development. Further screening of restorers of rvms, as well as crossing with a slow-growth line at normal temperature (24 °C), demonstrate that slowing of development overcomes the defects of rvms microspores and allows them to develop into functional pollen. Several other Arabidopsis TGMS lines were identified, and their fertility was also restored by slowing of development. Given that male reproductive development is conserved3, we propose that slowing of development is a general mechanism applicable to the sterility-fertility conversion of TGMS lines from different plant species.

19.
J Cancer Res Clin Oncol ; 146(2): 297-304, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31960187

RESUMO

PURPOSE: Itraconazole is an antifungal drug that has been clinically used for over 30 years. In recent years, scholars have discovered that it possesses an anticancer effect. Moreover, its mechanism has been clarified to some degree. What deserves to be mentioned is that itraconazole acting on the Hedgehog pathway has made a new progress in the treatment of cancers. While interestingly, studies have demonstrated that the Hedgehog pathway is largely activated in different cancer cells. RESULT: This review tries to highlight the effect of itraconazole on smoothened receptor (SMO) in the Hedgehog pathway, thereby reducing the glioma-associated oncogene homolog (GLI) release and finally exhibiting a range of anticancer effects, promoting apoptosis of cancer cells, and inhibiting proliferation by indirect inhibition of NF-κB pathway and inflammation, moreover, promoting the expression of cyclin-dependent kinase inhibitors, inhibiting the expression of target genes transcribed by GLI such as BCL-2 and Cyclin-D1. Besides, itraconazole increases the number of Bnip3, subsequently, inducing the dissociation of the Beclin-1/BCL-2 binding complex, as a result of ultimately promoting autophagy of cancer cells. CONCLUSION: As a new anticancer drug, whether itraconazole eventually entering clinical application requires the joint eforts of all scholars. In any case, an in-depth study on itraconazole will bring new hope for cancer patients in the near future.


Assuntos
Proteínas Hedgehog/metabolismo , Itraconazol/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Ensaios Clínicos Fase II como Assunto , Humanos , Itraconazol/uso terapêutico , Terapia de Alvo Molecular , Neoplasias/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened/metabolismo
20.
ACS Nano ; 14(1): 927-936, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31927974

RESUMO

Image-guided surgery plays a crucial role in realizing complete tumor removal, reducing postoperative recurrence and increasing patient survival. However, imaging of tumor lesion in the typical metabolic organs, e.g., kidney and liver, still has great challenges due to the intrinsic nonspecific accumulation of imaging probes in those organs. Herein, we report an in situ self-assembled near-infrared (NIR) peptide probe with tumor-specific excretion-retarded (TER) effect in tumor lesions, enabling high-performance imaging of human renal cell carcinoma (RCC) and achieving complete tumor removal, ultimately reducing postoperative recurrence. The NIR peptide probe first specifically recognizes αvß3 integrin overexpressed in renal cancer cells, then is cleaved by MMP-2/9, which is up-regulated in the tumor microenvironment. The probe residue spontaneously self-assembles into nanofibers that exhibit an excretion-retarded effect in the kidney, which contributes to a high signal-to-noise (S/N) ratio in orthotopic RCC mice. Intriguingly, the TER effect also enables precisely identifying eye-invisible tiny lesions (<1 mm), which contributes to complete tumor removal and significantly reduces the postoperative recurrence compared with traditional surgery. Finally, the TER strategy is successfully employed in high-performance identification of human RCC in an ex vivo kidney perfusion model. Taken together, this NIR peptide probe based on the TER strategy is a promising method for detecting tumors in metabolic organs in diverse biomedical applications.

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