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Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
MicroRNA delivery with osmotic polysorbitol-based transporter suppresses breast cancer cell proliferation
Muthunarayanan Muthiah1, Mohammad Ariful Islam2, Hwa-Jeong Lee1
1Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea.
Abstract:
MicroRNAs (miRNA) are short oligonucleotides of endogenous origin involved in post-transcriptional regulation and are altered in disease, making them potential therapeutic targets. miRNA replacement is necessary in cells with downregulated miRNAs levels in response to disease. miRNA 145 is a novel tumor suppressor gene involved in cell suppression, invasion and migration of cancer cells; it is downregulated in most cancers. Delivery of therapeutic miRNA using nanoparticles enhances the chances of successful delivery and expression of genes at the target site. We evaluated polysorbitol-mediated transporter (PSMT) in the cellular delivery of miRNA 145. The polysorbitol backbone possesses osmotic properties and leads to enhanced cellular uptake. PSMT delivers genes into cells by a caveolae-mediated endocytic pathway. Caveolae expression is usually altered in transformed cancer cells. Physicochemical characterization, and the transfection efficiency and transgene expression capability of PSMT/reporter plasmid DNA nanoparticles, were determined. GFP-tagged miRNA 145 delivery with PSMT was confirmed by confocal microscopy and Western blotting. The functional effects of miRNA 145 delivered with PSMT were analyzed by confocal microscopy, as well as in apoptosis, proliferation and wound healing assays. Finally, the expression of an miRNA 145 target protein, c-myc, was determined by Western blotting after intracellular delivery of PSMT/miRNA 145 nanoparticle (NP).
Insights
Polysorbitol-mediated transporter (PSMT) effectively delivers miRNA 145, a tumor suppressor, into cancer cells. This nanoparticle system shows promise for restoring miRNA levels and inhibiting cancer progression.
Area of Science:
- Molecular Biology
- Nanotechnology
- Cancer Research
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in various diseases, including cancer.
- miRNA replacement therapy is a potential strategy for diseases with downregulated miRNA levels.
- miRNA 145 acts as a tumor suppressor, but its expression is often reduced in cancers.
Purpose of the Study:
- To evaluate the efficacy of polysorbitol-mediated transporter (PSMT) for delivering miRNA 145 into cancer cells.
- To characterize the physicochemical properties and transfection efficiency of PSMT/miRNA 145 nanoparticles.
- To assess the functional impact of PSMT-delivered miRNA 145 on cancer cell behavior and target gene expression.
Main Methods:
- Nanoparticle formulation and physicochemical characterization of PSMT/miRNA 145.
- Confocal microscopy and Western blotting to confirm cellular uptake and expression of GFP-tagged miRNA 145.
- Functional assays including apoptosis, proliferation, and wound healing assays.
- Western blotting to determine the expression of the miRNA 145 target protein, c-myc.
Main Results:
- PSMT demonstrated efficient cellular uptake and delivery of GFP-tagged miRNA 145.
- Delivery of miRNA 145 via PSMT resulted in functional effects, including apoptosis induction and inhibition of proliferation and migration.
- PSMT/miRNA 145 nanoparticle treatment led to decreased expression of the c-myc protein, a known target of miRNA 145.
Conclusions:
- PSMT is an effective system for the cellular delivery of therapeutic miRNA 145.
- This nanoparticle-mediated delivery approach holds potential for cancer therapy by restoring tumor suppressor miRNA function.
- Further investigation into PSMT for miRNA-based cancer therapeutics is warranted.
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