An in-vivo study for targeted delivery of copper-organic complex to breast cancer using chitosan polymer nanoparticles

We have developed a strategy for targeted delivery of metal-diketo complex, bis(2,4-pentanedionato) copper(II) to breast cancer cells both in-vitro and in-vivo. This metal-organic complex induced ROS and subsequently DNA damage as well as mitochondrial membrane depolarization was observed. The mitochondria rupture further triggered apoptosis. For in-vitro targeting strategies, two different approaches were employed, folic acid or her-2 specific peptide (KCCYSL) was attached to stearic acid-modified polymeric Chitosan nanoparticles loaded with metal-organic complex bis(2,4-pentanedionato)copper(II). This was tested on two pairs of isogenic cells (FR+/FR- MCf-7 and her2+/her2- MCF-7) and it was observed that cells expressing the receptor were susceptible to the drug whereas non-expressing isogenic cells were almost un-affected. During in-vivo studies, mice receiving targeted delivery of bis(2,4-pentanedionato) copper (II) had increased survivability and reduced tumor volume compared to non-targeted drug delivery. During toxicity studies for liver enzymes it was also found that the mice receiving targeted drug did not show any sign of liver damage as well as other histology changes. (C) 2016 Elsevier B.V. All rights reserved.