Surface-targeting, ligand-switching nanoparticles for mitochondrial drug delivery in prostate cancer
Mentor: Omid Farokhzad, MD (Brigham and Women's Hospital)
An emerging method for targeting drugs to disease areas is to exploit the local changes that occur due to disease pathology and use these changes as triggers to improve targeting. This is accomplished by developing stimuli-responsive materials that change their physicochemical or drug-release properties upon encountering specific environmental cues, potentially leading to increased drug delivery to diseased tissues. These environmental cues may include low pH, inflammation, the presence of certain unique enzymes, and the reducing environment of endosomes. It may be possible to improve nanoparticle (NP) targeting to sites of disease by causing changes in NP surface properties at the target sites. In addition, the design of nanoparticles that can be internalized by endocytosis and thus release their active drugs inside subcellular organelles can be used to overcome multidrug resistance in cancer cells. In this project we develop surface switching NPs that can target first prostate cancer cells using a small molecule ligand and then the mitochondria specifically following endocytosis and endosomal release using a mitochondrial targeting peptide. This system would then be able to deliver its drug, which promotes pro-apoptosis signaling factors, directly to the mitochondria of the cell and create an efficient anti-cancer treatment.
Dual targeting, pH sensitive surface switching mitochondrial specific nanoparticle drug delivery system. This system delivers a drug which inhibits mitochondrial function and induces apoptosis in cancer cells. The drug is delivered directly to the mitochondria by (1) targeting PSMA overexpression on prostate cancer tumor cells and (2) after cellular uptake, escaping from the endosome using a pH sensitive surface switching mechanism and targeting the mitochondria of the cancer cells. Source: BWH Source: