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Anticarcinogenic effects of miR-199a-loaded gold nanoparticles on hepatocellular carcinoma: in vitro study
Samar El Achy1,2, Maisa E Moustafa3, Mohamed Fouad2,4
1Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria, 21521, Egypt.
Abstract:
Hepatocellular carcinoma (HCC) represents a critical oncological challenge demanding innovative therapeutic interventions. miRNA has been known to play an important role in cancer inhibition to control HCC's development and progression by regulating cell proliferation and apoptosis. The major hurdle is to deliver the miRNA at the site of tumor. Metallic nanoparticles with modified surface can be used to solve this problem. In the current study, gold-nanoparticles (Au NPs) were prepared, and their surface was modified with PEG moiety to facilitate the attachment of miRNA. For the first time, the modified gold NPs were loaded with miR-199a. Our findings revealed that, when cells treated with gold bare (80 nM) for 24 h, a low cytotoxicity was obtained (11.11 ± 2.25%). When cells treated with nanocomplex miRNA- PEG -Au NPs (80 nM) for 24 h, a significantly increased cellular cytotoxicity was obtained (55.7 ± 4.55%). Also, the prepared nanocomplex exhibits a promising potential in suppressing tumor cell proliferation and significantly enhancing apoptosis in a concentration and time dependent manner. These results underscore the transformative potential of targeted nanomaterial-based miRNA delivery as a sophisticated therapeutic modality in cancer management. In conclusion, Au NPs are excellent carriers for miRNA where they increase the cellular uptake, exerting a promising anticancer effect on HCC cells, representing a new approach in developing precision therapeutics for hepatocellular carcinoma.
Insights
Gold nanoparticles effectively deliver microRNA-199a to liver cancer cells, significantly increasing cancer cell death. This targeted delivery system shows promise for developing novel hepatocellular carcinoma (HCC) therapeutics.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) presents a significant oncological challenge requiring novel therapeutic strategies.
- MicroRNAs (miRNAs) are crucial regulators of cancer development, influencing cell proliferation and apoptosis.
- Efficient delivery of therapeutic miRNAs to tumor sites remains a major hurdle in cancer treatment.
Purpose of the Study:
- To develop and evaluate gold nanoparticles (Au NPs) as a delivery vehicle for miRNA in HCC treatment.
- To investigate the efficacy of surface-modified Au NPs loaded with miR-199a for targeting and treating HCC cells.
Main Methods:
- Gold nanoparticles (Au NPs) were synthesized and functionalized with polyethylene glycol (PEG) for miRNA attachment.
- The modified Au NPs were loaded with miR-199a to create a nanocomplex.
- Cytotoxicity assays were performed on HCC cells treated with bare Au NPs and the miRNA-PEG-Au NP nanocomplex.
Main Results:
- Bare Au NPs exhibited low cytotoxicity (11.11% ± 2.25%) at 80 nM.
- The miRNA-PEG-Au NP nanocomplex demonstrated significantly increased cellular cytotoxicity (55.7% ± 4.55%) at 80 nM.
- The nanocomplex suppressed tumor cell proliferation and enhanced apoptosis in a concentration- and time-dependent manner.
Conclusions:
- Surface-modified Au NPs serve as effective carriers for miRNA delivery in HCC.
- This targeted nanomaterial-based miRNA delivery system enhances cellular uptake and exerts a potent anticancer effect on HCC cells.
- The findings suggest a promising new approach for precision therapeutics in hepatocellular carcinoma management.
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