Smart drug delivery of p-Coumaric acid loaded aptamer conjugated starch nanoparticles for effective triple-negative breast cancer therapy

Abstract

The nano-drug delivery system utilizing the ligand functionalized nanoparticles have a tremendous application in cancer therapeutics. The present study was aimed to fabricate the p-Coumaric acid-loaded aptamer (ligand) conjugated starch nanoparticles (Apt-p-CA-AStNPs) for effective treatment of triple-negative breast cancer (MDA-MB-231). The FT-IR spectrum showed the presence of functional groups associated with para-Coumaric acid (p-CA) and amino starch (AS) in p-CA-AStNPs. Further, the conjugation of aptamer in p-CA-AStNPs was confirmed by agarose gel electrophoresis. Transmission electron microscopic analysis revealed that the synthesized Apt-p-CA-AStNPs were less agglomerated. The zeta size analyzer displayed the average particle size of 218.97 ± 3.07 nm with ȥ-potential -29.2 ± 1.35 mV, and PDI 0.299 ± 0.05 for Apt-p-CA-AStNPs. The drug encapsulation and loading efficiencies were 80.30 ± 0.53% and 10.35 ± 0.85% respectively for Apt-p-CA-AStNPs. Apt-p-CA-AStNPs showed a rapid and bursting release in the initial five hours of the experiment in pH 5.4. A significant change was found in their cytotoxic efficacy between the samples: p-CA, p-CA-AStNPs, and Apt-p-CA-AStNPs. Among the tested samples, Apt-p-CA-AStNPs caused higher cytotoxicity in MDA-MB-231 cells through ROS regulation, nuclear damage, mitochondrial membrane potential, and apoptosis-related protein expressions. Overall, these results proved that Apt-p-CA-AStNPs were efficiently inhibited the MDA-MB-231 cells by regulating apoptosis.

Keywords: Aptamer; Cancer therapy; Drug delivery; Nanoformulation; p-Coumaric acid.