Aptamer-Functionalized Nanoparticles Mediate PD-L1 siRNA Delivery for Effective Gene Silencing in Triple-Negative...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Effective delivery of small interfering RNA (siRNA) is crucial for cancer therapies.
• Tumor-targeting requires ligands for receptor-mediated endocytosis into cancer cells.
• Aptamers are suitable ligands for functionalizing nanocarriers for targeted delivery.

Purpose of the Study:

• To design a novel aptamer-based platform for active delivery of siRNA targeting programmed cell death-ligand 1 (PD-L1) to triple-negative breast cancer (TNBC) cells.
• To create nanovectors capable of specific cell targeting and efficient cargo delivery.

Main Methods:

• Developed PLGA-based polymeric nanoparticles loaded with PD-L1 siRNA.
• Conjugated nanoparticles with a novel RNA aptamer specific for TNBC and resistant to nucleases.
• Evaluated siRNA uptake and PD-L1 expression suppression in vitro.

Main Results:

• Aptamer-conjugated nanoparticles demonstrated specific uptake into TNBC cells (MDA-MB-231, BT-549), not non-TNBC cells (BT-474).
• Efficient endosomal release of siRNA was observed.
• Achieved almost complete suppression of PD-L1 expression within 90 minutes of cell treatment.

Conclusions:

• The aptamer-based nanoparticle platform enables targeted siRNA delivery to TNBC cells.
• This strategy offers a promising approach for optimizing siRNA delivery systems for TNBC treatment.
• The developed nanovectors show high specificity and efficiency in targeting and downregulating PD-L1.