Targeted TP53 and KRAS Modulation Via AuNP-Mediated RNA Delivery Suppresses Cancer Progression

Area of Science:

• Biotechnology
• Molecular Biology
• Cancer Research

Background:

• Small RNAs are crucial for gene regulation, including transcriptional activation and gene silencing.
• Their specificity makes them valuable for studying gene function, disease mechanisms, and developing therapies.

Purpose of the Study:

• To develop a gold nanoparticle (AuNP)-based RNA delivery system.
• To enhance the stability and cellular uptake of therapeutic small RNAs targeting KRAS and TP53 pathways.

Main Methods:

• AuNPs were synthesized and conjugated with KRAS-targeting siRNA and p53-stimulating saRNA.
• A549 and HCT116 cells were transfected with the AuNP-RNA conjugates.
• Gene expression, cell cycle, apoptosis, proliferation, migration, and invasion were analyzed.

Main Results:

• AuNP-conjugated siRNA downregulated KRAS, while AuNP-conjugated saRNA upregulated TP53.
• Co-delivery of both RNAs via AuNPs significantly increased TP53 levels without affecting KRAS.
• The dual delivery system induced cell cycle arrest, enhanced apoptosis, and reduced proliferation, migration, and invasion.

Conclusions:

• AuNP-mediated co-delivery of siRNA and saRNA effectively modulates the KRAS-p53 signaling axis.
• This approach shows enhanced therapeutic potential for KRAS-mutant, TP53-wild-type cancers.
• Further in vivo studies are needed to assess clinical feasibility.