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Yuting Yang, Xiaowei Tai, Kairong Shi, Shaobo Ruan, Yue Qiu, Zhirong Zhang, Bing Xiang, Qin He
The enhanced permeability and retention (EPR) effect has been comfortably accepted, and extensively assumed as a keystone in the research on tumor-targeted drug delivery system. Due to the unsatisfied tumor-targeting efficiency of EPR effect being one conspicuous drawback, nanocarriers that merely relying on EPR effect are difficult to access the tumor tissue and consequently trigger efficient tumor therapy in clinic. In the present contribution, we break up the shackles of EPR effect on nanocarriers thanks to their universal distribution characteristic...
2016: Theranostics
Yijun Zhang, Youguang Luo, Rui Lyu, Jie Chen, Ruming Liu, Dengwen Li, Min Liu, Jun Zhou
Cell migration, a complex process critical for tumor progression and metastasis, requires a dynamic crosstalk between microtubules (MTs) and focal adhesions (FAs). However, the molecular mechanisms underlying this event remain elusive. Herein we identify the proto-oncogenic protein Src as an important player in the regulation of the MT-FA crosstalk. Src interacts with and phosphorylates end-binding protein 1 (EB1), a member of MT plus end-tracking proteins (+TIPs), both in cells and in vitro. Systematic mutagenesis reveals that tyrosine-247 (Y247) is the primary residue of EB1 phosphorylated by Src...
2016: Theranostics
Christoph Tondera, Sandra Hauser, Anne Krüger-Genge, Friedrich Jung, Axel T Neffe, Andreas Lendlein, Robert Klopfleisch, Jörg Steinbach, Christin Neuber, Jens Pietzsch
Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation)...
2016: Theranostics
Jinxie Zhang, Xudong Zhang, Gan Liu, Danfeng Chang, Xin Liang, Xianbing Zhu, Wei Tao, Lin Mei
The inner membrane vesicle system is a complex transport system that includes endocytosis, exocytosis and autophagy. However, the details of the intracellular trafficking pathway of nanoparticles in cells have been poorly investigated. Here, we investigate in detail the intracellular trafficking pathway of protein nanocapsules using more than 30 Rab proteins as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy. We observed that FITC-labeled protein nanoparticles were internalized by the cells mainly through Arf6-dependent endocytosis and Rab34-mediated micropinocytosis...
2016: Theranostics
Xiao Bao, Ming-Wei Wang, Jian-Min Luo, Si-Yang Wang, Yong-Ping Zhang, Ying-Jian Zhang
Objective: Antiangiogenesis therapy (AAT) has provided substantial benefits regarding improved outcomes and survival for suitable patients in clinical settings. Therefore, the early definition of therapeutic effects is urgently needed to guide cancer AAT. We aimed to optimize the early response monitoring and prediction of AAT efficacy, as indicated by the multi-targeted anti-angiogenic drug sunitinib in U87MG tumors, using noninvasive positron emission computed tomography (PET) molecular imaging strategies of multifactorial bioparameters...
2016: Theranostics
Lichan Tao, Yihua Bei, Ping Chen, Zhiyong Lei, Siyi Fu, Haifeng Zhang, Jiahong Xu, Lin Che, Xiongwen Chen, Joost Pg Sluijter, Saumya Das, Dragos Cretoiu, Bin Xu, Jiuchang Zhong, Junjie Xiao, Xinli Li
Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes...
2016: Theranostics
Chao Li, Sitong Du, Yiping Lu, Xiaowei Lu, Fangwei Liu, Ying Chen, Dong Weng, Jie Chen
Long term pulmonary exposure to crystalline silica leads to silicosis that manifests progressive interstitial fibrosis, eventually leading to respiratory failure and death. Despite efforts to eliminate silicosis, clinical cases continue to occur in both developing and developed countries. The exact mechanisms of crystalline silica-induced pulmonary fibrosis remain elusive. Herein, we find that 4-1BB is induced in response to crystalline silica injury in lungs and that it is highly expressed during development of experimental silicosis...
2016: Theranostics
Xiao Tong, Zhantong Wang, Xiaolian Sun, Jibin Song, Orit Jacobson, Gang Niu, Dale O Kiesewetter, Xiaoyuan Chen
Gold nanorods (AuNR) have been intensively used in nanomedicine for cancer diagnostics and therapy, due to their excellent plasmonic photothermal properties. Tuning the size and aspect ratio of AuNR tailors the localized surface plasmon resonance (LSPR) in the NIR spectrum at which biological tissues are transparent, thus enables specific and effective treatment. The AuNR extravasates into tumor interstitium through enhanced permeation and retention (EPR) effect. Efficient AuNR based cancer therapy requires efficient AuNR tumor delivery...
2016: Theranostics
Shadi A Esfahani, Pedram Heidari, Sun A Kim, Shuji Ogino, Umar Mahmood
Purpose: To assess optical imaging of Mesenchymal-Epithelial Transition factor (MET) for delineation and characterization of intrahepatic models of human hepatocellular carcinoma (HCC) and metastatic colorectal cancer (CRC), and thereby demonstrate its potential use in precision oncology. Materials and Methods: MET expression in human CRC and HCC was assessed in tissue microarrays. We used GE-137, a modified cyanine 5-tagged peptide for MET targeting. HepG2 and Huh-7 (HCC) and HT-29 (CRC) cells with MET overexpression, and LNCaP cells (negative control) with minimal MET expression were incubated with the probe...
2016: Theranostics
Jenq-Lin Yang, Wei-Yu Chen, Yin-Ping Chen, Chao-Ying Kuo, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage...
2016: Theranostics
Honglin Jin, Yuan Qian, Yanfeng Dai, Sha Qiao, Chuan Huang, Lisen Lu, Qingming Luo, Jing Chen, Zhihong Zhang
Dendritic cell (DC) migration to the lymph node is a key component of DC-based immunotherapy. However, the DC homing rate to the lymphoid tissues is poor, thus hindering the DC-mediated activation of antigen-specific T cells. Here, we developed a system using fluorescent magnetic nanoparticles (α-AP-fmNPs; loaded with antigen peptide, iron oxide nanoparticles, and indocyanine green) in combination with magnetic pull force (MPF) to successfully manipulate DC migration in vitro and in vivo. α-AP-fmNPs endowed DCs with MPF-responsiveness, antigen presentation, and simultaneous optical and magnetic resonance imaging detectability...
2016: Theranostics
Mathilde Cheray, Romain Pacaud, Arulraj Nadaradjane, Lisa Oliver, François M Vallette, Pierre-François Cartron
DNA methylation is a fundamental feature of genomes and is a candidate for pharmacological manipulation that might have important therapeutic advantage. Thus, DNA methyltransferases (DNMTs) appear to be ideal targets for drug intervention. By focusing on interactions existing between DNMT3A and DNMT3A-binding protein (D3A-BP), our work identifies the DNMT3A/ISGF3γ interaction such as a biomarker whose the presence level is associated with a poor survival prognosis and with a poor prognosis of response to the conventional chemotherapeutic treatment of glioblastoma multiforme (radiation plus temozolomide)...
2016: Theranostics
Nasim Nosoudi, Aniqa Chowdhury, Steven Siclari, Saketh Karamched, Vaideesh Parasaram, Joe Parrish, Patrick Gerard, Narendra Vyavahare
Degeneration of elastic lamina and vascular calcification are common features of vascular pathology such as aortic aneurysms. We tested whether dual therapy with targeted nanoparticles (NPs) can remove mineral deposits (by delivery of a chelating agent, ethylene diamine tetraacetic acid (EDTA)) and restore elastic lamina (by delivery of a polyphenol, pentagalloyl glucose (PGG)) to reverse moderate aneurysm development. EDTA followed by PGG NP delivery led to reduction in macrophage recruitment, matrix metalloproteinase (MMP) activity, elastin degradation and calcification in the aorta as compared to delivery of control blank NPs...
2016: Theranostics
Kalyani Ektate, Ankur Kapoor, Danny Maples, Ahmet Tuysuzoglu, Joshua VanOsdol, Selvarani Ramasami, Ashish Ranjan
Ultrasound imaging is widely used both for cancer diagnosis and to assess therapeutic success, but due to its weak tissue contrast and the short half-life of commercially available contrast agents, it is currently not practical for assessing motion compensated contrast-enhanced tumor imaging, or for determining time-resolved absolute tumor temperature while simultaneously reporting on drug delivery. The objectives of this study were to: 1) develop echogenic heat sensitive liposomes (E-LTSL) and non-thermosensitive liposomes (E-NTSL) to enhance half-life of contrast agents, and 2) measure motion compensated temperature induced state changes in acoustic impedance and Laplace pressure of liposomes to monitor temperature and doxorubicin (Dox) delivery to tumors...
2016: Theranostics
Yanli Jin, Yiwu Yao, Li Chen, Xiaohui Zhu, Bei Jin, Yingying Shen, Juan Li, Xin Du, Yuhong Lu, Sheng Jiang, Jingxuan Pan
Quiescent leukemia stem cells (LSCs) that are insensitive to BCR-ABL tyrosine kinase inhibitors confer resistance to imatinib in chronic myelogenous leukemia (CML). Identifying proteins to regulate survival and stemness of LSCs is urgently needed. Although histone deacetylase inhibitors (HDACis) can eliminate quiescent LSCs in CML, little is known about the underlying mechanism that HDACis kill LSCs. By fishing with a biotin-labeled probe, we identified that HDACi JSL-1 bound to the protein γ-catenin. γ-Catenin expression was higher in LSCs from CML patients than normal hematopoietic stem cells...
2016: Theranostics
Xiang Qi, Kevin Tak-Pan Ng, Yan Shao, Chang Xian Li, Wei Geng, Chang Chun Ling, Yuen Yuen Ma, Xiao Bing Liu, Hui Liu, Jiang Liu, Wai Ho Yeung, Chung Mau Lo, Kwan Man
BACKGROUND AND AIMS: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth. GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study. Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation. METHODS: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established...
2016: Theranostics
Reinier Hernandez, Haiyan Sun, Christopher G England, Hector F Valdovinos, Emily B Ehlerding, Todd E Barnhart, Yunan Yang, Weibo Cai
Overexpression of CD146 has been correlated with aggressiveness, recurrence rate, and poor overall survival in hepatocellular carcinoma (HCC) patients. In this study, we set out to develop a CD146-targeting probe for high-contrast noninvasive in vivo positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging of HCCs. YY146, an anti-CD146 monoclonal antibody, was employed as a targeting molecule to which we conjugated the zwitterionic near-infrared fluorescence (NIRF) dye ZW800-1 and the chelator deferoxamine (Df)...
2016: Theranostics
Yi Shuai, Li Liao, Xiaoxia Su, Yang Yu, Bingyi Shao, Huan Jing, Xinjing Zhang, Zhihong Deng, Yan Jin
Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging...
2016: Theranostics
Bingdi Chen, Wenjun Le, Yilong Wang, Zhuoquan Li, Dong Wang, Lei Ren, Ling Lin, Shaobin Cui, Jennifer J Hu, Yihui Hu, Pengyuan Yang, Rodney C Ewing, Donglu Shi, Zheng Cui
A set of electrostatically charged, fluorescent, and superparamagnetic nanoprobes was developed for targeting cancer cells without using any molecular biomarkers. The surface electrostatic properties of the established cancer cell lines and primary normal cells were characterized by using these nanoprobes with various electrostatic signs and amplitudes. All twenty two randomly selected cancer cell lines of different organs, but not normal control cells, bound specifically to the positively charged nanoprobes...
2016: Theranostics
Shuyi Wang, Chunxiao Zhang, Guozhou Wang, Boran Cheng, Yulei Wang, Fangfang Chen, Yuanyuan Chen, Maohui Feng, Bin Xiong
Circulating tumor cells (CTCs) have been considered as the origin of cancer metastasis. Thus, detection of CTCs in peripheral blood is of great value in different types of solid tumors. However, owing to extremely low abundance of CTCs, detection of them has been technically challenging. To establish a simple and efficient method for CTCs detection in patients with hepatocellular carcinoma (HCC), we applied biocompatible and transparent HA/CTS (Hydroxyapatite/chitosan) nanofilm to achieve enhanced topographic interactions with nanoscale cellular surface components, and we used sLex-AP (aptamer for carbohydrate sialyl Lewis X) to coat onto HA/CTS nanofilm for efficient capture of HCC CTCs, these two functional components combined to form our CTC-(BioT)Chip platform...
2016: Theranostics
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