Silencing c-myc gene by siRNA delivered by cationic niosomes in MCF-7 cells
Shatha N Abdeljaber1, Alaa A Aljabali2, Bahaa Altrad1
1Department of Biological Science, Faculty of Science, Yarmouk University, 21163 Irbid, Jordan.
Objectives:
Gene therapy has a strong potential to treat different cancer types cancers with high therapeutic outcomes. c-myc is believed to be responsible for more than 15% of all gene regulation and functions as a transcription factor for proteins essential for cell proliferation. This study aimed to develop niosome nanocarriers to knockdown c-myc expression using anti-c-myc short-interfering RNA (siRNA) in MCF-7 cells. Altering the activity of the c-myc proto-oncogene has been identified as an important element in minimizing cancer cell growth because anti-c-myc siRNA degrades c-myc mRNA.
Methods:
Noisomes were prepared from Tween 85, cholesterol, and didodecyldimethylammonium bromide at 50:40:10 and 40:40:20 molar ratios. Anti-c-myc siRNA was loaded in the prepared niosomes and then applied on MCF-7 cells.
Key Findings:
Niosomes had a total positive charge formed electrostatic interactions with siRNA. Niosomes were spherical with a size range of 70-100 nm. The prepared niosomes were nontoxic to MCF-7 cells, with IC50 values of >250 µg/ml for both formulations. After encapsulation of anti-c-myc siRNA, nioplexes reduced c-myc mRNA expression by more than 50% compared with the untreated cells. Empty niosomes did not affect c-myc mRNA expression levels, indicating that the effect was due to siRNA rather than the particles themselves.
Conclusions:
This study provides evidence that niosomes can function as suitable carriers for siRNA delivery to knockdown the c-myc oncogene in MCF-7 cells, thus reducing cancer cell growth.
Insights
Niosome nanocarriers effectively delivered anti-c-myc siRNA to reduce cancer cell growth by downregulating c-myc mRNA expression. These niosomes show promise for gene therapy applications in cancer treatment.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- c-myc proto-oncogene is a key regulator of cell proliferation, implicated in over 15% of cancers.
- Gene therapy offers potential for cancer treatment by targeting oncogenes.
- Short-interfering RNA (siRNA) can degrade specific mRNA, including c-myc mRNA, to inhibit cancer growth.
Purpose of the Study:
- To develop niosome nanocarriers for delivering anti-c-myc siRNA.
- To evaluate the efficacy of niosomes in delivering anti-c-myc siRNA to MCF-7 cells.
- To assess the impact of c-myc knockdown on cancer cell growth.
Main Methods:
- Niosomes were formulated using Tween 85, cholesterol, and didodecyldimethylammonium bromide.
- Anti-c-myc siRNA was loaded into the prepared niosomes.
- Niosome-siRNA complexes (nioplexes) were applied to MCF-7 cells for evaluation.
Main Results:
- Niosomes exhibited electrostatic interactions with siRNA, forming spherical particles (70-100 nm) with a positive charge.
- The niosomes demonstrated low toxicity to MCF-7 cells (IC50 >250 µg/ml).
- Encapsulated anti-c-myc siRNA significantly reduced c-myc mRNA levels by over 50% in MCF-7 cells.
Conclusions:
- Niosomes are effective carriers for siRNA delivery.
- Niosomes facilitate the knockdown of the c-myc oncogene in cancer cells.
- This approach holds potential for reducing cancer cell proliferation via gene therapy.
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