Cell Death & Disease
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2024
·Vol. 15
·期 10
·1-10
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IF 8.1
Li Ming-Qiao,He Yu-Qi,Zhang Meng-Ni,Tang Wan,Tan Ya,Cheng Yue,Yang Mei,Zhao Nan,Li Ling,Yu Si-Rui,Li Ruo-Lan,Pan Qiong,Wu Ming-Yue,Chai Jin
Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 8
·2209-2218
·
IF 5.831
Siqi Wang,Wenzhi Ren,Jianhua Wang,Zhenqi Jiang,Madiha Saeed,Lili Zhang,Aiguo Li,Aiguo Wu
At present, transmembrane glycoprotein CD133 highly expressed pancreatic cancer stem cells (PCSCs), with the features of chemotherapeutic/radiotherapeutic resistance and exclusive tumorigenic potential, are considered as the primary cause of metastasis and recurrence in pancreatic cancer, and therefore are an effective target in the disease treatment. Furthermore, with the launch of precision medicine, multifunctional nanoprobes have been applied as an efficient strategy for the magnetic resonance imaging (MRI)-guided photothermal therapy (PTT) of pancreatic cancer. In this research, with the aim of achieving precise MRI-guided PTT in CD133 highly expressed PCSCs, novel bTiO2-Gd-CD133mAb nanoprobes were designed and successfully prepared by loading Gd-DOTA and CD133 monoclonal antibodies on black TiO2 nanoparticles. It was very interesting to find that the r1 relaxivity value of the nanoprobes was 34.394 mM−1 s−1, about 7.5 times that of commercial Magnevist (4.5624 mM−1 s−1), which indicates that the nanoprobes have good potential as MRI T1 contrast agents with excellent performance. Herein, CD133 highly expressed PANC-1 cells were selected and verified as PCSCs model. In vitro experiments demonstrated that the nanoprobes exhibited active-targeting ability in PANC-1 cells, and consequently could specially enhance T1-weighted MR imaging and 808 nm near-infrared (NIR)-triggered PTT efficiency in the PCSCs model. Our study not only provides a new strategy for the effective treatment of pancreatic cancer and its’ stem cells, but also further broadens the application of black TiO2 in the field of cancer theranostics.
研究领域:
癌症研究
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纳米技术
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医学成像
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诊疗一体化
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2018
·
IF 5.08
Yiqun Wang,Yi Lu,Jinkang Gong,Yuan Yao
Intermediate filaments, together with actin microfilaments and microtubules constituent the cytoskeleton of mammalian cells, involving in various cellular activities. The roles of intermediate filaments in cell skeleton reorganization when responding with extracellular matrix (ECM) nanostructure are poorly understood yet. To unveil the effects of fibrous composition and orientation on cells, we developed electrospun nanofibers of varying topology and components, and the effects on assembly of intermediate filaments as keratin and vimentin were investigated in detail. We found that aligned nanofibers enhanced expression of E-cadherin and promoted assembly of keratin intermediate filaments. Meanwhile, the compositional variation show different preference on up-regulation of the two intermediate filaments. Compared to keratin, the assembly of vimentin intermediate filaments were promoted by incorporating bovine serum albumin (BSA) functionalized graphene oxide (BSA-GO) into polycaprolactone (PCL) nanofibers. Thus, our findings elucidate how the different physical factors of fibrous extracellular matrix affect the reorganization of cytoskeleton by assembly of keratin and vimentin intermediate filaments.
研究领域:
材料科学
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细胞生物学
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癌症研究
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纳米技术
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2017
·
IF 7.504
Xuefang Ding,Yujie Su,Cheng Wang,Fangrong Zhang,Kerong Chen,Yu Wang,Min Li,Wei Wang
Single-walled carbon nanotubes (SWNTs) with unique physicochemical properties have exhibited promising biomedical applications as drug and gene carriers. In this study, polyethylenimine (PEI)-modified SWNT conjugates linked with candesartan (CD) were developed to deliver vascular endothelial growth factor (VEGF)-targeted siRNA (siVEGF) for the synergistic and targeted treatment of tumor angiogenesis. The characterization results revealed that SWNT–PEI–CD conjugates were successfully synthesized and exhibited desirable dispersibility and superior stability. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) results showed that SWNT–PEI–CD/siVEGF complexes could achieve high cellular uptake and specific intracellular distribution of siRNA in AT1R overexpressed PANC-1 cells. Strong down-regulation of VEGF was also verified by qualitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot in complex-treated PANC-1 cells. The in vitro angiogenesis assay showed that SWNT–PEI–CD/siVEGF complexes highly inhibited tube formation of human umbilical vein endothelial cells. Furthermore, in vivo observation in PANC-1 xenografted nude mice demonstrated that SWNT–PEI–CD/siVEGF complexes exhibited significant distribution at tumor sites and caused obvious inhibition of tumor growth and tumor-associated angiogenesis repression induced by the drug combination of CD and siVEGF. Finally, a WST-1 assay indicated that SWNT–PEI–CD possessed low cytotoxicity, and a hemolysis test showed good biocompatibility of SWNT–PEI–CD. Hematological and histological analyses confirmed that SWNT–PEI–CD/siVEGF complexes did not cause any obvious toxic effects to blood and major organs. These findings suggested that the SWNT–PEI–CD/siVEGF co-delivery system with tumor-targeting specificity, improved endosomal escaping properties, and collaboration of angiogenesis inhibition could be a prospective method for efficient tumor antiangiogenic therapy.
研究领域:
癌症生物学
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纳米医学
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药学
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分子生物学
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DOI
PubMed
高影响因子
DRUG DELIVERY
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2019
·
IF 3.829
Lei Fang,Wei Zhang,Zhen Wang,Xinxin Fan,Ziting Cheng,Xiaoya Hou,Daquan Chen
Stability in systemic circulation, effective tumor accumulation, and the subsequent crucial subcellular targeting are significant elements that maximize the therapeutic efficacy of a drug. Accordingly, novel nanoparticles based on polysaccharides that simultaneously presented prolonged systemic circulation and mitochondrial-targeted drug release were synthesized. First, the mitochondrial-targeted polymer, 3,4-dihydroxyphenyl propionic acid-chitosan oligosaccharide-dithiodipropionic acid-berberine (DHPA-CDB), was synthesized, which was used to form self-assembled curcumin (Cur)-encapsulated cationic micelles (DHPA-CDB/Cur). Negatively charged oligomeric hyaluronic acid-3-carboxyphenylboronic acid (oHA-PBA), a ligand to sialic acid and CD44, was further added to the surface of the preformed DHPA-CDB/Cur core to shield the positive charges and to prolong blood persistence. oHA-PBA@DHPA-CDB/Cur formed a covalent polyplex of oHA-PBA and DHPA-CDB/Cur via the pH-responsive borate ester bond between PBA and DHPA. The mildly acidic tumor environment led to the degradation of borate ester bonds, thereby realizing the exposure of the cationic micelles and causing a charge reversal from −19.47 to +12.01 mV, to promote cell internalization and mitochondrial localization. Compared with micelles without the oHA-PBA modification, the prepared oHA-PBA@DHPA-CDB/Cur showed enhanced cytotoxicity to PANC-1 cells and greater cellular uptake via receptor-mediated endocytosis. oHA-PBA@DHPA-CDB/Cur was effectively targeted to the mitochondria, which triggered mitochondrial membrane depolarization. In mice xenografted with PANC-1 cells, compared with control mice, oHA-PBA@DHPA-CDB/Cur resulted in more effective tumor suppression and greater biosafety with preferential accumulation in the tumor tissue. Thus, the long-circulating oHA-PBA@DHPA-CDB/Cur, with mitochondrial targeting and tumor environment charge-reversal capabilities, was shown to be an excellent candidate for subcellular-specific drug delivery.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
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