Aptamer conjugated and oleuropein loaded PLGA nanoparticles increase the apoptosis of breast cancer cells.

Newer therapeutic strategies aim to increase the sensitivity of cancer cells to apoptosis. The phytochemical, oleuropein (OLP) has shown promising anticancer properties; however, its low bioavailability and non-specific delivery limit its anticancer potential. Therefore, we developed a novel aptamer-conjugated nanocarrier delivery system for the targeted, efficient and controlled delivery of OLP to the MDA-MB-231 breast cancer cells. The oleuropein-loaded nanoparticles (OLP-NPs) were synthesized, characterized, and conjugated with a Mucin-1 specific aptamer (APT) (APT-OLP-NPs) for an efficient delivery of OLP. Characterized APT-OLP-NPs formulation exhibited a small hydrodynamic diameter and negative zeta potential driving the efficient cellular uptake. The increases nanoparticle size following the aptamer conjugation as compared to the OLP-NPs, confirmed the successful surface functionalization. The latter supported the targeting ability of the developed formulation. APT-OLP-NPs significantly reduced MDA-MB-231 cell viability and induced apoptosis as confirmed by the changes seen in the relative mRNA expression of apoptosis-related genes, including Bcl-2 family members. Protein-level analysis validating the transcripts expression of immune markers suggested that this anticancer effect of OLP is driven by Akt1 signaling. This pathway controls the expression of NF-κB and guides the transcription factor FOXO1 to regulate apoptosis. Overall, our findings demonstrate increased apoptosis in aggressive breast cancer cells.