Modulation of mitochondrial membrane permeability transition pore by Annonaceous acetogenins (ACGs)-Loaded Transferrin Conjugated Nanoparticles

Abstract

Making the optimal cancer treatment choice can be challenging and more challenging is harnessing the therapeutic potential of bioactive molecules isolated from plants. The mitochondrion is the main organelle of oxidative stress in cells. Increased permeability of the inner mitochondrial membrane is a key phenomenon in cell death. The protein transferrin (Tf) was conjugated to the NPs with the role to actively targeting them to the cancerous cells. Peg-GNPs, Tf-GNPs, Peg-G-ACGs and Tf-Peg-G-ACGs were successfully synthesized by probe sonication method and yielded NPs with size about 100 nm, with polydispersity index around 0.20 and a negative zeta potential of about − 30 mV. Mitochondria, isolated from rat liver were exposed to different concentrations of Tf-peg-G-ACGs. Their ability to induce mitochondrial permeability transition (mPT) pore opening were assessed spectrophotometrically. In the absence of CaCl2, Tf-peg-G-ACGs caused a concentration-dependent induction of mPT pore opening by 13, 11.3, 8.7, and 2.7 folds, at concentrations 10, 20,50 and 100 μg/mL, respectively, when compared with the control with no attendant inhibitory activity which was intensified in the presence of Calcium to 22, 19.7, 15 and 8.3 folds at concentrations 10, 20,50 and 100 μg/mL, respectively. Tf-peg-G-ACGs showed improved ability to induced mitochondrial membrane pore opening which can be explored for the treatment of cancer.