The Novel Method for Delivery miRNA-34a: a New Cationic PEGylated Niosomal Formulation for the Treatment of Breast Cancer

Author(s):  
Najmeh Alsadat Abtahi ◽  
Fateme Haghiralsadat ◽  
Abolghasem Siyadatpanah ◽  
Javad Zavar Reza ◽  
Veeranoot Nissapatorn ◽  
...  

Abstract Background: The reactive surface of nanoparticles makes it possible to simply modify with a biocompatible coating and load with therapeutic agents such as siRNA, miRNA, an anti-cancer drug, and antibody. MicroRNAs, like the noncoding RNAs, contribute critical to the regulation of numerous cellular functions via transcriptional silencing. MicroRNAs (miRNAs) have enormous potential in cancer treatment, however, it is difficult to deliver them effectively to most solid tumors. The encapsulation of miRNA-34a in niosome nanoparticles is an attractive strategy for biopharmaceutical resources against cancer. The present study investigated the effectiveness of anticancer activity against MCF-7 and T47D human breast adenocarcinoma cells of a new noiosome system composed of nonionic surfactants. Methods: We used the optimum formulations to transfer miRNA-34a to breast cancer cells, providing potential benefits, such as exceptionally high entrapment efficiency (almost 100%), spherical shape, suitable positive charge (zeta potential~ + 24 mV) and small diameter (~100 nm). Results: The miRNA-34a-niosomes represented improved cytotoxic activity against the cancer cells compared to readily dispersed miRNA-34a. The resulting data indicate that delivery of miRNA-34a via niosome can affect tumor suppression, highlighting its promising anticancer effects in breast cancer cells. Conclusion: In conclusion, the developed a new carrier to improve the delivery of miRNA-34a into the tumor cells. The formulation provided in the present work is stable with a sustained release, high efficiency of miRNA-34a loading having a diameter of 115 nm. miRNA loading is performed without potentially harmful chemical reactions. Niosomes loaded with miRNA-34a in this study represented significant cytotoxic effects against the human breast cancer MCF-7 and T47D cells, which highlights their potential effect on this type of cancer cells.

Author(s):  
Firdos Alam Khan ◽  
Sultan Akhtar ◽  
Sarah Ameen Almofty ◽  
Dana Almohazey ◽  
Munthar Alomari

Breast cancer treatment mostly revolved around radiation therapy and surgical interventions, these treatments doesn’t provide satisfactory relief to the patients and carry unmanageable side-effects. Nanomaterials show promising results in treating cancer cells and have many advantages such as high biocompatibility, bioavailability and effective therapeutic capabilities. Interestingly, fluorescent magnetic nanoparticles have been used in many biological and diagnostic applications, but there is no report of use of fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in the treatment of human breast cancer cells. In the present study, we have tested the effect FMSP-nanoparticles on human breast cancer cells (MCF-7). We have tested different concentrations (1.25µg/1mL, 12.5µg/mL and 50µg/1mL) of FMSP-nanoparticles in MCF-7 cells and evaluated the nanoparticles response morphometrically. Our results revealed that FMSP-nanoparticles produced a concentration dependent effect on the cancer cells, dose of 1.25µg/mL produced no significant effect on the cancer cell morphology and cell death, whereas dosages of 12.5µg/mL and 50µg/mL respectively showed significant nuclear augmentation, disintegration, chromatic condensation followed by dose dependent cell death. Our results demonstrate FMSP-nanoparticles have ability to induce cell death in MCF-7 cells and may be considered as a potential anti-cancer agent for breast cancer treatments.


2018 ◽  
Vol 16 (2) ◽  
pp. 127-137
Author(s):  
Paula Sofia Coutinho Medeiros ◽  
Ana Lúcia Marques Batista de Carvalho ◽  
Cristina Ruano ◽  
Juan Carlos Otero ◽  
Maria Paula Matos Marques

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.


2003 ◽  
Vol 17 (10) ◽  
pp. 2002-2012 ◽  
Author(s):  
Olga A. Sukocheva ◽  
Lijun Wang ◽  
Nathaniel Albanese ◽  
Stuart M. Pitson ◽  
Mathew A. Vadas ◽  
...  

Abstract Current understanding of cytoplasmic signaling pathways that mediate estrogen action in human breast cancer is incomplete. Here we report that treatment with 17β-estradiol (E2) activates a novel signaling pathway via activation of sphingosine kinase (SphK) in MCF-7 breast cancer cells. We found that E2 has dual actions to stimulate SphK activity, i.e. a rapid and transient activation mediated by putative membrane G protein-coupled estrogen receptors (ER) and a delayed but prolonged activation relying on the transcriptional activity of ER. The E2-induced SphK activity consequently activates downstream signal cascades including intracellular Ca2+ mobilization and Erk1/2 activation. Enforced expression of human SphK type 1 gene in MCF-7 cells resulted in increases in SphK activity and cell growth. Moreover, the E2-dependent mitogenesis were highly promoted by SphK overexpression as determined by colony growth in soft agar and solid focus formation. In contrast, expression of SphKG82D, a dominant-negative mutant SphK, profoundly inhibited the E2-mediated Ca2+ mobilization, Erk1/2 activity and neoplastic cell growth. Thus, our data suggest that SphK activation is an important cytoplasmic signaling to transduce estrogen-dependent mitogenic and carcinogenic action in human breast cancer cells.


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