# Development of Small Interfering RNA Loaded Cationic Lipid Nanoparticles for the Treatment of Liver Cancer with Elevated α-Fetoprotein Expression

## TL;DR

Scientists developed cationic lipid nanoparticles to deliver siRNA targeting α-fetoprotein in liver cancer cells, effectively reducing tumor growth and inducing cell death.

## Contribution

A novel cationic lipid nanoparticle delivery system for siRNA targeting α-fetoprotein in liver cancer is developed.

## Key findings

- Cationic lipid nanoparticles showed high siRNA encapsulation efficiency (>95%) and efficient cell entry.
- siAFP-loaded nanoparticles silenced AFP mRNA and increased apoptotic cell death via caspase-3/7 activation.
- The cLNPs demonstrate potential as a targeted therapeutic strategy for liver cancer treatment.

## 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.