Targeted Delivery of Betulinic Acid to Cancer Cell Mitochondria by Using Gold Nanoparticles

Abstract

Globally, cancer is the biggest cause of mortality. Currently, breast cancer ranks fifth in terms of cancer-related mortality and is one of the most often diagnosed cancers. Conventional therapies have their limits. Drug delivery systems and many other approaches have been developed to address challenges such as hormone therapy, stem cell therapies, micelles, and nanoparticles. Specifically, nanoparticles engineered with multiple functionalities stand out as a promising solution to overcome various barriers associated with targeted delivery. Gold nanoparticles with a diameter of around 4 nm were synthesized using a two-phase method. The nanoparticle surface was subsequently modified with Polyethylene Glycol (PEG) to facilitate the loading of the hydrophobic drug Betulinic Acid. UV visible spectroscopy, Raman spectroscopy and FTIR analysis confirm the surface modification. We introduce these nanoparticles into the mitochondria of cancerous cells and initiate apoptosis. The outcomes of the MTT assay revealed that gold nanoparticles, modified with Polyethylene Glycol (PEG) and loaded with Betulinic Acid (BA), exhibited greater toxicity toward MDA-MB-231 cells as compared to HEK-293 cells. The modification of gold nanoparticles enhanced the suppressive impact of BA on MDA-MB-231 cells, primarily attributed to increased accumulation of reactive oxygen species (ROS) and caused change in mitochondrial membrane potential (MMP)