Active Targeting Nanotheranostic System for Dual-Modality Imaging-Guided Chemo-/Photodynamic Therapy of Pancreatic Cancer

2021 ◽  
Author(s):  
Yong Han ◽  
Qiusha Tang ◽  
Gang Jia ◽  
Yanli An ◽  
Yinan Ding
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Monoclonal Antibody ◽  
Mesoporous Silica ◽  
Synergistic Effects ◽  
Synergetic Effect ◽  
Dual Modality ◽  
Dual Modality Imaging

Abstract Background: Pancreatic cancer (PC) is one of the most devastating types of cancers worldwide and has a remarkably poor survival rate, emphasizing the need for more effective strategies for the diagnosis and therapy of PC. Upconversion nanoparticles (UCNPs) have gained a privileged place in the biomedical field due to their outstanding properties. Besides, epithelial cell adhesion molecule (EpCAM) as one of the key biomarkers of pancreatic cancer stem cells, is a vital target for theranostic, diagnostic, and/or therapeutic intervention in nanomedicine. In this study, the theranostic nanosystem (EpCAM-UCMSNs-MX) was formed from the mesoporous silica-coated UCNPs functionalized with anti-EpCAM monoclonal antibody, and then one anticancer drug and photosensitizer, mitoxantrone (MX), was loaded into the mesoporous silica. The nanotheranostic system was used to target caner stem cells for realizing simultaneous dual-modality MR/UCL imaging and synergetic chemotherapy and NIR-triggered PDT. Results: After conducting series of characterizations, the nanotheranostic systems own superior uniform sphericity and long-time stability. In vitro and vivo experiments show the nanocomposites have good biocompatibility and can target caner stem cells to realize simultaneous dual-modality MR/UCL imaging. Furthermore, in comparison with UCMSNs-MX and free MX, MX-loaded UCMSNs conjugated with anti-EpCAM monoclonal antibody (EpCAM-UCMSNs-MX) are efficiently endocytosed by cancerous cells and show synergetic effect with PDT in vitro. In vivo experiments reconfirm the synergistic effects observed with the combination of EpCAM-UCMSNs-MX and PDT, which results in better treatment outcomes as compared to chemotherapy or NIR irradiation alone that fail to show any noticeable systemic toxicity.Conclusions: The resulting nanotheranostics were shown to target caner stem cells to confer simultaneous dual-modality MR/UCL imaging and induced intracellular reactive oxygen species exposed to 980 nm excitation, leading to synergetic chemotherapy and NIR-triggered PDT. These results offer a promising strategy for designing a multifunctional nanotheranostic system for dual-modality imaging-guided synergistic oncotherapy.

scholarly journals Initial in vitro and in vivo assessment of Au@DTDTPA-RGD nanoparticles for Gd-MRI and 68Ga-PET dual modality imaging

2015 ◽  
Vol 2 (Suppl 1) ◽  
pp. A89 ◽  
Author(s):  
Charalmpos Tsoukalas ◽  
Gautier Laurent ◽  
Gloria Jiménez Sánchez ◽  
Theodoros Tsotakos ◽  
Rana Bazzi ◽  
...  
Keyword(s):  
Dual Modality ◽  
Dual Modality Imaging ◽  
In Vivo Assessment

scholarly journals Targeting the EZH2-PPAR Axis Is a Potential Therapeutic Pathway for Pancreatic Cancer

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Jilong Hu ◽  
Zhinan Zheng ◽  
Jia Lei ◽  
Yuxin Cao ◽  
Qiyun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
Synergistic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonist ◽  
Combined Use

Enhancer of zeste homolog 2 (EZH2) is abnormally highly expressed in pancreatic cancer (PC). However, it is not ideal to treat PC by inhibiting EZH2. This study reported that the combined use of pan-peroxisome proliferator-activated receptor (PPAR) agonist could significantly improve the anti-PC effect of EZH2 inhibitor. In vitro, PC cell lines PANC-1 and AsPC-1 were cultured, and MTT and flow cytometry were performed to observe the effects of pan-PPAR agonist bezafibrate and EZH2 selective inhibitor GSK126 on cell viability and apoptosis. In vivo, CDXs of PANC-1 and AsPC-1 were established to observe the effects of bezafibrate and GSK126 on bearing tumors. Western blotting was performed to detect the protein expressions of H3K27me3, β-catenin, p-β-catenin, cyclin D1, c-Myc, and cleaved caspase 3 in vitro and in vivo. The results showed that bezafibrate significantly improved the effects of GSK126 on proliferation inhibition and apoptosis promotion in vitro and the growth suppression of CDX tumors in vivo. It also significantly enhanced the effects of GSK126 on upregulating the expression level of p-β-catenin and that of cleaved caspase 3 in vitro and in vivo. In parallel, downregulation of the expression levels of H3K27me3, β-catenin, cyclin D1, and c-Myc was also observed in vitro or in vivo. These results suggest that the combination of bezafibrate and GSK126 has synergistic effects on PC, and the molecular mechanism may be related to the enhanced inhibition of the Wnt/β-catenin signaling pathway. We believe that targeting the EZH2-PPAR axis is a potential therapeutic pathway for PC.

scholarly journals Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cells Properties Cultured by a Novel 3D Semi-Solid System

2018 ◽  
Vol 47 (5) ◽  
pp. 2109-2125 ◽  
Author(s):  
Zhaocong Yang ◽  
Yanfeng Zhang ◽  
Tingting Tang ◽  
Qinhua Zhu ◽  
Wanyue Shi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Culture System ◽  
High Throughput Sequencing ◽  
Semi Solid ◽  
Pancreatic Cancer Stem Cells ◽  
Solid System

Background/Aims: Pancreatic cancer remains one of the deadliest human malignancies, the lethality of which may be attributed to the presence of pancreatic cancer stem cells (PCSCs), a small subpopulation of cells existing within pancreatic tumor with high carcinogenesis. Therefore, it is crucial to establish an efficient enrichment and culture system of PCSCs and identify the key genes involved in the regulation of PCSCs. The three-dimensional (3D) liquid suspension mammosphere culture system has been established for enrichment and culture of PCSCs in vitro as the cell spheres are likely to originate from individual cell clone, but it has been challenged because the cell spheroids could be a result of cell aggregation. Methods: We optimized the existing culture system by adding methylcellulose to create a 3D semi-solid system which prevented the non-specific aggregation. Then we identified the CSC properties of Panc-1 spheroid cells cultured by this system by detecting the genes associated with stemness and by evaluation of the tumorigenicity in vitro and in vivo through invasion, migration and xenograft experiments methods. Subsequently, we performed high-throughput sequencing (HTS) of the Panc-1 spheroid cells. Results: We confirmed the PCSCs properties and high malignancy of the Panc-1 spheroid cells enriched by our novel 3D semi-solid system both in vitro and in vivo. Hundreds of mRNA, microRNA (miRNA) and dozens of long non-coding RNA (LncRNA) were identified to be differentially regulated in PCSCs-like Panc-1 spheroid cells compared with their parental cells by HTS. Conclusions: Our results demonstrate an efficient enrichment and culture system for Panc-1 spheroid cells with the PCSCs properties. The differentially expressed genes and their targets identified by the HTS of the Panc-1 spheroid cells can serve as new potential biomarkers for pancreatic cancer diagnosis and targeted therapy.

In vitro and in vivo comparison of DTPA- and DOTA-conjugated antiferritin monoclonal antibody for imaging and therapy of pancreatic cancer

2007 ◽  
Vol 34 (3) ◽  
pp. 293-304 ◽  
Author(s):  
Emmanuelle N. Sabbah ◽  
Jean Kadouche ◽  
David Ellison ◽  
Ciara Finucane ◽  
Didier Decaudin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Monoclonal Antibody

scholarly journals Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Shui Ma ◽  
Xiao-Li Yang ◽  
Yu-Shan Liu ◽  
Hua Ding ◽  
Jian-Jun Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Loss Of Function ◽  
Self Renewal

Abstract Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

scholarly journals microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3

2021 ◽  
Author(s):  
Jian Chang ◽  
Hanjun Li ◽  
Zhongchao Zhu ◽  
Pei Mei ◽  
Weimin Hu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Extracellular Vesicles ◽  
Stem Cell Differentiation ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
Invasion And Migration ◽  
Oct4 Expression

Abstract Aim Given the fact that tumor-associated macrophage-derived extracellular vesicles (EVs) are attributable to tumor aggressiveness, this research intends to decode the mechanism of M2 macrophage-derived EVs in the differentiation and activities of pancreatic cancer (PaCa) stem cells via delivering microRNA (miR)-21-5p. Methods Polarized M2 macrophages were induced, from which EVs were collected and identified. miR-21-5p expression in M2 macrophage-derived EVs was tested. After cell sorting, CD24+CD44+EpCAM+ stem cells were co-cultured with M2 macrophages, in which miR-21-5p was upregulated or downregulated. The effects of M2 macrophage-derived EVs and miR-21-5p on Nanog/octamer-binding transcription factor 4 (Oct4) expression, sphere formation, colony formation, invasion and migration capacities, apoptosis, and in vivo tumorigenic ability were examined. Krüppel-like factor 3 (KLF3) expression and its interaction with miR-21-5p were determined. Results M2 macrophage-derived EVs promoted PaCa stem cell differentiation and activities. miR-21a-5p was upregulated in M2 macrophage-derived EVs. miR-21a-5p downregulation in M2 macrophage-derived EVs inhibited Nanog/Oct4 expression and impaired sphere-forming, colony-forming, invasion, migration, and anti-apoptosis abilities of PaCa stem cells in vitro and tumorigenic ability in vivo. miR-21-5p targeted KLF3 to mediate the differentiation and activities of PaCa stem cells, and KLF3 was downregulated in PaCa stem cells. Conclusion This work explains that M2 macrophage-derived exosomal miR-21a-5p stimulates differentiation and activity of PaCa stem cells via targeting KLF3, paving a novel way for attenuating PaCa stemness. Graphical abstract

Decidua-derived mesenchymal stem cells as carriers of mesoporous silica nanoparticles. In vitro and in vivo evaluation on mammary tumors

2016 ◽  
Vol 33 ◽  
pp. 275-282 ◽  
Author(s):  
Juan L. Paris ◽  
Paz de la Torre ◽  
Miguel Manzano ◽  
M. Victoria Cabañas ◽  
Ana I. Flores ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Mammary Tumors ◽  
In Vivo Evaluation

scholarly journals Artificial Stem Cells Mediated Inflammation-Tropic Delivery of Antiviral Drugs for Pneumonia Treatment

2021 ◽  
Author(s):  
Aiping Qin ◽  
Sheng Chen ◽  
Songpei Li ◽  
Xiaotao Huang ◽  
Yinshan Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Synergistic Effects ◽  
Immune Deficiency Syndrome ◽  
Deficiency Syndrome ◽  
Antiviral Drugs ◽  
Viral Dna ◽  
Marrow Mesenchymal Stem Cells ◽  
Low Efficiency

Abstract Background: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals including transplant recipients and Acquired Immune Deficiency Syndrome patients. Currently, antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity.Methods: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo.Results: MPDGP showed significant inflammation tropism and efficient suppression of both viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects by combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. Conclusion: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cells to deliver the antiviral drugs for pneumonia treatment.

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