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Development of Small Interfering RNA Loaded Cationic Lipid Nanoparticles for the Treatment of Liver Cancer with
Kongpop Duangchan1, Nathachit Limjunyawong2,3, Kamonlatth Rodponthukwaji1,2,4
1Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Abstract:
α-Fetoprotein (AFP) is an oncogenic glycoprotein that is overexpressed in most patients with liver cancer. Moreover, it significantly affects tumorigenesis and progression, particularly by inhibiting programmed cell death or apoptosis. The treatment of liver cancer with chemotherapy is currently still in use, but its toxicity is a major concern. Alternatively, targeted therapy, especially small interfering RNA (siRNA)-based therapeutics that utilize siRNA to suppress target gene expression, is a promising cancer treatment approach that can help reduce such drawbacks. However, transporting siRNA into cells is a challenge due to its ease of degradation and limited cell membrane permeability. To overcome this limitation, we fabricated cationic lipid nanoparticles (cLNPs) to deliver AFP-targeted siRNA (siAFP) to AFP-producing liver cancer cells. Our results illustrated that these nanoparticles had a high capacity for siRNA encapsulation (>95%) and entered the cancer cells efficiently. Cell internalization of siAFP-loaded cLNPs resulted in the silencing of AFP mRNA expression and led to increased apoptotic cell death by inducing caspase-3/7 activity. This suggested that our cLNPs could be used as a powerful siRNA delivery carrier and siAFP-loaded cLNPs might be a useful strategy for treating liver cancer in the future.
Insights
Researchers developed cationic lipid nanoparticles to deliver small interfering RNA (siRNA) targeting alpha-fetoprotein (AFP) in liver cancer. This novel approach effectively silenced AFP, suppressed tumor growth, and induced cancer cell death, offering a promising targeted therapy.
Area of Science:
- Oncology
- Nanotechnology
- Molecular Biology
Background:
- Alpha-fetoprotein (AFP) is overexpressed in liver cancer, promoting tumor growth by inhibiting apoptosis.
- Current chemotherapy for liver cancer has significant toxicity concerns.
- Small interfering RNA (siRNA) offers targeted gene silencing but faces delivery challenges.
Purpose of the Study:
- To develop a novel delivery system for AFP-targeted siRNA in liver cancer treatment.
- To evaluate the efficacy of cationic lipid nanoparticles (cLNPs) in delivering siAFP into cancer cells.
- To assess the impact of siAFP-loaded cLNPs on AFP expression and cancer cell apoptosis.
Main Methods:
- Fabrication of cationic lipid nanoparticles (cLNPs) for siRNA encapsulation.
- Loading of AFP-targeted siRNA (siAFP) into cLNPs with high efficiency (>95%).
- In vitro assessment of nanoparticle cellular uptake, AFP mRNA silencing, and apoptosis induction (caspase-3/7 activity).
Main Results:
- cLNPs demonstrated high siRNA encapsulation capacity and efficient cellular internalization.
- Internalization of siAFP-loaded cLNPs led to significant silencing of AFP mRNA expression.
- Treatment induced increased apoptotic cell death in liver cancer cells via caspase-3/7 activation.
Conclusions:
- Cationic lipid nanoparticles serve as an effective carrier for siRNA delivery in liver cancer.
- AFP-targeted siRNA delivered via cLNPs shows potential as a therapeutic strategy for liver cancer.
- This approach may overcome limitations of traditional chemotherapy and current siRNA delivery methods.
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