Engineering of Nanoparticles for Mitochondrial Trafficking of Therapeutics and Diagnosis of Cardiovascular Diseases
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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 nano-medical platforms for simultaneous targeting, imaging, and combination therapy administration. We are developing hybrid nanoparticle (NP) systems such as hybrids of polymeric–gold nanoparticle and polymeric–iron oxide hybrid nanoparticle for their potential use in combination therapy of cancer and image-guided therapy of atherothrombotic vascular disease (ATVD), respectively. Mitochondrial dysfunctions cause many human disorders. A platform technology of carrying bioactive molecules to the mitochondrial matrix could be of enormous potential benefit in therapeutics. We are developing a rationally designed mitochondria-targeted NP system and its optimization for efficient delivery of a variety of mitochondria-acting therapeutics by blending a targeted poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-triphenylphosphonium (PLGA-b-PEG-TPP) polymer with either non-targeted PLGA-b-PEG-OH or PLGA-COOH. 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. Apoptosis of cells along the arterial wall serves as a target for detection of plaque vulnerable to embolism. In this context, to detect atherosclerotic plaques noninvasively, we are developing MRI active NPs which can selectively target macrophages in the arteries and detect apoptotic cells with altered or compromised membranes. These highly engineered NPs include iron oxide in the core of a polymeric matrix for MRI detection, mannose for macrophage targeting, apoptotic cell targeting peptides, and a metal binding site for effective detection. The utility of these NPs in the diagnosis of atherosclerosis will be discussed.
- Nano@Tech Lecture Series