Project title: Development of Cancer-cell Targeted Cytochrome c-based Smart Nanoparticles
Our efforts are directed towards the development of novel cytochrome c-based theranostic drug-delivery systems. The inactivation of the upstream components of the signaling pathways (such as the p53 pathway) that activate the release of cytochrome c (Cyt c) from the mitochondria to the cytoplasm in response to DNA damage avoid the apoptosis mechanism in many cancer cells. To overcome this, we aim at delivering Cyt c to the cytoplasm of cancer cells. Recently, we demonstrated that Cyt c nanoparticles were able to induce programmed cell death in an in vitro cell culture study using HeLa cells. These nanoparticles consisted of a Cyt c core stabilized by a cover consisting of PLGA, a biodegradable and biocompatible FDA approved polymer. Herein, we extend this study by transforming the system into an active delivery system. The ligand chosen, folate, was linked to poly(ethylene glycol) (FA-PEG) and that to PLGA in order to target folate over-expressing cells. The constructs will be tested by in vitro tests using folate receptor positive and negative cancer cell lines as model systems. We are also interested in studying the potential of our nanoparticles, which are based on a cationic protein coated with a polymer mainly composed of PLGA, to cross through a difficult biological barrier like the BBB. To address such questions, experiments ongoing in our laboratory focus on in vivo experiments using animal models in collaboration with Dr. Kucheryavykh from the Universidad Central del Caribe.
To contact Dr. Griebenow you can write to the bellow address
E-mail: kai.griebenow@gmail.com