Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/ijms232012666
Keywords
hepatocellular carcinoma (HCC); alpha-fetoprotein (AFP); small interfering RNA (siRNA); angiogenesis inhibitor; nanoparticle (NP); polylactic-co-glycolic acid (PLGA)
Funding
- NSRF via the Program Management Unit for Human Resource and Institutional Development, Research and Innovation [B16F640132]
- Research Network NANOTEC (RNN) program of the National Nanotechnology Center (NANOTEC), NSTDA, Ministry of Higher Education, Science, Research and Innovation (MHESI), Thailand
- Chalermphrakiat grant, the Faculty of Medicine Siriraj Hospital, Mahidol University
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Angiogenesis inhibitor drugs have limitations in cancer therapy, but combination therapy with small interfering RNA (siRNA) loaded nanoparticles (NPs) could enhance therapeutic efficacy. This study successfully synthesized AFP-siRNA-loaded NPs and demonstrated their synergistic effect with angiogenesis inhibitors in decreasing cell viability in hepatocellular carcinoma (HCC). The combination treatment also significantly silenced AFP-mRNA expression, further enhancing the therapeutic outcomes.
Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (AFP-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The AFP siRNA-loaded NPs were successfully synthesized at an average size of 242.00 +/- 2.54 nm. Combination treatment of AFP-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. AFP-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 +/- 2.72 and 44.04 +/- 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that AFP-siRNA incorporated with NPs could significantly silence AFP-mRNA expression compared to unloaded NPs. Interestingly, the expression level of AFP-mRNA was further decreased to 28.53 +/- 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.
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