Research

Mitochondrial transplantation is an innovative strategy that can restore favorable metabolic phenotypes in cells with aberrant energy metabolism. My laboratory synthesized a polymer conjugate composed of dextran and triphenylphosphonium (Dex-TPP) for the purpose of functionalization of isolated mitochondria. Mitochondrial transfer to breast cancer and cardiovascular cells profoundly impacted cellular respiration, mediating a shift towards improved oxidative phosphorylation. Our findings represent the first demonstration of polymer functionalization of isolated mitochondria.

Short-term pharmacokinetics limit the efficacy of cardiac pharmacotherapies. We adapted the dry pericardial puncture to access the pericardial sac for nanoparticle (NP)-based drug delivery to the heart and were one of the first labs to demonstrate the potential of exploiting the pericardial space for NP-based drug delivery to the heart (J Control Release 2017, 262). We showed long-term presence of NPs in the heart following pericardial delivery, and extensive intramural penetration and maintenance of released payload, converting the pericardial space into a local drug delivery depot to the heart and addressing the limitations of pericardial drug delivery and other local delivery strategies.

Fenestrated vasculature contributes immensely to heightened accumulation of NPs in tumors through the enhanced permeability and retention (EPR) effect. Importantly, “leaky” vasculature is present in other diseases. Hearts undergoing heart failure have endothelial dysfunction, and we demonstrated heightened particle accumulation in mice undergoing heart failure (Eur J Heart Fail, 2016, 18, 2). Similarly, endothelial remodeling exists in pulmonary arterial hypertension (PAH) and we demonstrated increased NP accumulation in a preclinical model of PAH (Int J Pharm, 2017, 524, 1-2).

Nanoparticle-based drug and gene delivery remains an active area of research in the laboratory.

Many cardiovascular interventions, including stent deployment and balloon angioplasty, are currently performed under x-ray guidance. This modality is associated with poor soft tissue contrast, the inability to properly navigate endovascular tools, and significant safety concerns in patients due to exposure to ionizing radiation and iodinated contrast agents. Magnetic resonance imaging (MRI) is a safe modality that offers high-resolution anatomic and physiologic information, and interventional CMR (iCMR) has the potential to allow for more accurate navigation and positioning of catheter-based devices, all in a radiation-free environment. However, the promise of iCMR has not translated into a clinical reality due to the scarcity of MR-compatible devices. Thus, our objective is to create application-specific, iCMR-compatible devices, and demonstrate the potential of iCMR by performing cardiovascular catheterization procedures using these devices. Work in this area was recently published in the journal Biomedical Microdevices (2019, 20, 2).