Abstract

The potential benefits of integrating nanomaterials with properties such as biodegradability, magnetization, fluorescence, and near-infrared absorption into a single object of nanoscale dimensions can lead to the development of hybrid nanocarrier platforms for simultaneous targeting, imaging, and combination therapy administration. We are developing hybrid nanoparticle (NP) systems for their potential use in organelle targeting, combination therapy of cancer, and image-guided therapy of atherothrombotic vascular diseases.

Mitochondrial dysfunctions cause many human disorders. A platform technology for carrying bioactive molecules to different mitochondrial compartments could be of enormous potential benefit in medicine. We are developing rationally designed, programmable NP platform for diagnosis and targeted delivery of therapeutics for mitochondrial dysfunction related diseases. An optimized formulation for maximal mitochondrial uptake was identified through in vitro screening of a library of charge and size varied NPs and the uptake was studied by qualitative and quantitative investigations of cytosolic and mitochondrial fractions of cells treated with mitochondria-targeted blended NPs. The versatility of this platform was demonstrated by studying a variety of mitochondria-acting therapeutics for different applications. These include mitochondria targeting chemotherapeutics for cancer, mitochondrial antioxidant for disease of central nervous system, and mitochondrial uncoupler for obesity. On the cardiovascular front, we are developing a long- circulating hybrid NP platform to selectively target macrophages and sense apoptosis for detection of plaque vulnerable to embolism.