Polyethylenimine-coated gold-magnetic nanoparticles for ADAM10 siRNA delivery in prostate cancer cells

2020 ◽  
Vol 35 (6) ◽  
pp. 504-516
Author(s):  
Raju Panday ◽  
Ahmed ME Abdalla ◽  
Yu Miao ◽  
Xiaohong Li ◽  
Manisha Neupane ◽  
...  

For an effective medical application of therapeutic siRNA, a safe and an efficient delivery system are required. Herein, magnetic nanoparticles (MNPs) have been successfully used as siRNA delivery vehicles. Firstly, MNPs were coated with gold (Au) nanoparticles and then capped with PEI. To improve the biocompatibility of nanoparticles, hyaluronic acid (HA) was coated onto the surface of PEI-Au/Fe nanoparticles. The prepared HA-PEI-Au/Fe3O4 nanoparticles were characterized and found to be uniform and well segregated in TEM analysis. FTIR analysis confirmed that HA was successfully conjugated to PEI. The polymer content in these nanoparticles was relatively higher than PEG coated nanoparticles. Cell viability assay demonstrated that the nanoparticles were relatively biocompatible in nature. ADAM10 siRNA was loaded into the HA-PEI-Au/Fe3O4 nanoparticles and cytotoxicity to prostate cancer (PC3) cells was analyzed. The results indicate that ADAM10 siRNA loaded HA-PEI-Au/Fe3O4 suppress the PC3 cells growth in vitro. Clearly, it could be confirmed that HA-PEI coated Au/Fe3O4 nanoparticles with higher biocompatibility appear to be suitable for intracellular siRNA delivery.

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xupeng Mu ◽  
Haibin Lu ◽  
Lianlian Fan ◽  
Shaohua Yan ◽  
Kebang Hu

Gene silencing using small interfering RNA (siRNA) has shown significant potential in the treatment of cancer. Herein, we developed the lipid-polymer hybrid nanoparticles (PEG-LP/siRNA NPs) for siRNA delivery. The cell viability assay indicated that PEG-LP/siRNA NPs had negligible cell cytotoxicity. The cellular uptake efficiency of PEG-LP/siRNA NPs measured by flow cytometry was up to 94.4%. Importantly, in vitro gene knockdown experiments demonstrated that PEG-LP/siJnk-1 NPs could significantly downregulate the expression of Jnk-1 at both the mRNA and protein levels in DU145 cells. Gene knockdown of Jnk-1 could activate apoptosis in part by the mitochondrial pathway in DU145 cells. Moreover, the PEG-LP/siJnk-1 NPs could inhibit tumor growth in a DU145 xenograft murine model, suggesting its therapeutic promise in cancer therapy.


2019 ◽  
Vol 34 (7) ◽  
pp. 952-964 ◽  
Author(s):  
Raju Panday ◽  
Ahmed Mohammed Elamin Abdalla ◽  
Miao Yu ◽  
Xiaohong Li ◽  
Chenxi Ouyang ◽  
...  

2019 ◽  
Vol 26 (12) ◽  
pp. 887-892
Author(s):  
Cynarha Daysy Cardoso da Silva ◽  
Cristiane Moutinho Lagos de Melo ◽  
Elba Verônica Matoso Maciel Carvalho ◽  
Mércia Andréa Lino da Silva ◽  
Rosiely Félix Bezerra ◽  
...  

Background: Lectins have been studied in recent years due to their immunomodulatory activities. Objective: We purified a lectin named OniL from tilapia fish (Oreochromis niloticus) and here we analyzed the cell proliferation and cytokine production in Balb/c mice splenocytes. Methods: Cells were stimulated in vitro in 24, 48, 72 hours and 6 days with different concentrations of OniL and Con A. Evaluation of cell proliferation was performed through [3H]-thymidine incorporation, cytokines were investigated using ELISA assay and cell viability assay was performed by investigation of damage through signals of apoptosis and necrosis. Results: OniL did not promote significant cell death, induced high mitogenic activity in relation to control and Con A and stimulated the cells to release high IL-2 and IL-6 cytokines. Conclusion: These findings suggest that, like Con A, OniL lectin can be used as a mitogenic agent in immunostimulatory assays.


2021 ◽  
Vol 22 (13) ◽  
pp. 7063
Author(s):  
Sharon Mordechay ◽  
Shaun Smullen ◽  
Paul Evans ◽  
Olga Genin ◽  
Mark Pines ◽  
...  

Progressive loss of muscle and muscle function is associated with significant fibrosis in Duchenne muscular dystrophy (DMD) patients. Halofuginone, an analog of febrifugine, prevents fibrosis in various animal models, including those of muscular dystrophies. Effects of (+)/(−)-halofuginone enantiomers on motor coordination and diaphragm histopathology in mdx mice, the mouse model for DMD, were examined. Four-week-old male mice were treated with racemic halofuginone, or its separate enantiomers, for 10 weeks. Controls were treated with saline. Racemic halofuginone-treated mice demonstrated better motor coordination and balance than controls. However, (+)-halofuginone surpassed the racemic form’s effect. No effect was observed for (−)-halofuginone, which behaved like the control. A significant reduction in collagen content and degenerative areas, and an increase in utrophin levels were observed in diaphragms of mice treated with racemic halofuginone. Again, (+)-halofuginone was more effective than the racemic form, whereas (−)-halofuginone had no effect. Both racemic and (+)-halofuginone increased diaphragm myofiber diameters, with no effect for (−)-halofuginone. No effects were observed for any of the compounds tested in an in-vitro cell viability assay. These results, demonstrating a differential effect of the halofuginone enantiomers and superiority of (+)-halofuginone, are of great importance for future use of (+)-halofuginone as a DMD antifibrotic therapy.


2020 ◽  
Vol 11 (1) ◽  
pp. 319-327
Author(s):  
Chenlin Xu ◽  
Zijian Xiao ◽  
Heng Wu ◽  
Guijuan Zhou ◽  
Duanqun He ◽  
...  

AbstractBackgroundAlzheimer’s disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of β-amyloid protein (Aβ) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated.MethodsIn this study, SK-N-SH cells were used to establish an in vitro model to investigate the effects of BDMC on the Aβ1–42-induced neurotoxicity. SK-N-SH cells were pretreated with BDMC and with or without compound C and EX527 for 30 min after co-incubation with rotenone for 24 h. Subsequently, western blotting, cell viability assay and SOD and GSH activity measurement were performed.ResultsBDMC increased the cell survival, anti-OS ability, AMPK phosphorylation levels and SIRT1 in SK-N-SH cells treated with Aβ1–42. However, after treatment with compound C, an AMPK inhibitor, and EX527, an SIRT1inhibitor, the neuroprotective roles of BDMC on SK-N-SH cells treated with Aβ1–42 were inhibited.ConclusionThese results suggest that BDMC exerts a neuroprotective role on SK-N-SH cells in vitro via AMPK/SIRT1 signaling, laying the foundation for the application of BDMC in the treatment of neurodegenerative diseases related to AMPK/SIRT1 signaling.


2013 ◽  
Vol 14 (7) ◽  
pp. 13577-13591 ◽  
Author(s):  
Wennan Zhao ◽  
Wenzhi Guo ◽  
Qianxiang Zhou ◽  
Sheng-Nan Ma ◽  
Ran Wang ◽  
...  

Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 508 ◽  
Author(s):  
Daniela Luz ◽  
Maria Amaral ◽  
Flavia Sacerdoti ◽  
Alan Bernal ◽  
Wagner Quintilio ◽  
...  

Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible for causing hemolytic uremic syndrome (HUS), a life-threatening thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and acute renal failure after bacterially induced hemorrhagic diarrhea. Until now, there has been neither an effective treatment nor method of prevention for the deleterious effects caused by Stx intoxication. Antibodies are well recognized as affinity components of therapeutic drugs; thus, a previously obtained recombinant human FabC11:Stx2 fragment was used to neutralize Stx2 in vitro in a Vero cell viability assay. Herein, we demonstrated that this fragment neutralized, in a dose-dependent manner, the cytotoxic effects of Stx2 on human glomerular endothelial cells, on human proximal tubular epithelial cells, and prevented the morphological alterations induced by Stx2. FabC11:Stx2 protected mice from a lethal dose of Stx2 by toxin-antibody pre-incubation. Altogether, our results show the ability of a new encouraging molecule to prevent Stx-intoxication symptoms during STEC infection.


1994 ◽  
Vol 53 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Michael Untch ◽  
Bernd-Uwe Sevin ◽  
James P. Perras ◽  
Roberto Angioli ◽  
Andrea Untch ◽  
...  

2020 ◽  
Vol 17 (36) ◽  
pp. 871-883
Author(s):  
Moath Kahtan BASHIR ◽  
Yasser Fakri MUSTAFA ◽  
Mahmood Khudhayer OGLAH

Cancer constitutes one of the most severe public health menaces worldwide. It is imperative to synthesize new compounds and explore their antitumor activity to find a potential resolution to this health problem. Synthesis of new scaffolds and evaluating their antitumor activity is a relevant approach for combating cancer development. Coumarins can exhibit diverse biological activities, and one of these is the antitumor activity. This study aimed to synthesize new coumarins by grafting their precursors to the aromatic amines via Schiff base formation and evaluating their introductory antitumor activity. New multifunctional coumarins (MC1-MC9) were prepared by integrating a functionalized coumarin with different toluidine derivatives via a Schiff-base linkage. Spectral characterization inspired by FTIR, 1H- and 13C- NMR spectroscopies has established the chemical structures of the synthesized products. The antitumor activity was explored in vitro versus four dominant human cancer lines, including HeLa, SKG, MCF-7, and AMN3. The outcomes acquired from the cell viability assay inspected by applying MTT dye have revealed that the synthesized multifunctional coumarins, particularly MC3, have a hopeful activity. It can be concluded that a similar trend of activity against the test cell lines was observed for the synthesized coumarins, with the best action being versus MCF-7 and the least one versus AMN3. This study not only affords a new scaffold of a significant antitumor activity but also provides some insights into its structureactivity relationship.


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