Development and Characterization of PEG-b-PPS Nanocarriers for Magnetic Resonance Imaging and Drug Delivery


Like many diseases, atherosclerotic cardiovascular disease is driven by the activity of inflammatory cells. Using molecular imaging to target and analyze populations of inflammatory cells is one promising strategy to non-invasively assess atherosclerosis progression. However, current molecular imaging contrast agents are not suited for such targeted imaging applications. Nanomaterial-based strategies have great promise for targeted delivery of contrast agents due to their ability to accumulate within target cells, specifically in immune cell subsets. In particular, the diblock co-polymer poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) is a versatile nanomaterial system capable of self-assembling into nanocarriers of different shapes and has great utility for the targeted delivery of encapsulated cargo to immune cells. This work describes the development of PEG-b-PPS nanocarriers for the delivery of magnetic resonance imaging (MRI) contrast agents in the context of targeted imaging of atherosclerotic cardiovascular disease. First, I have demonstrated the utility of multiple PEG-b-PPS nanocarrier morphologies for encapsulation and controlled delivery of metal ferrite magnetic nanostructures (MNS), which are nanoscale MRI contrast agents for T2-weighted imaging. I focused on developing MNS-encapsulated bicontinuous nanospheres (MBCNs), and characterizing their MRI contrast enhancement, ability to deliver therapeutic payloads in vitro and in vivo, and response to oxidative stimuli. Notably, I found that MBCNs undergo a transition in morphology into MNS-loaded micelles under oxidative conditions, which makes these nanocarriers promising for sustained delivery applications. Second, I engineered PEG-b-PPS polymersomes (PS) to simultaneously (i) deliver Gd-DOTA for T1 MRI contrast enhancement and (ii) display the P-D2 peptide sequence for targeting dendritic cells (DCs) in atherosclerotic plaques. My work demonstrated that DOTA-displaying PS (DOTA-PS) are promising nanocarriers for T1 MRI, demonstrating effective T1 enhancement in vitro. I further characterized the use of the P-D2 peptide for mediating effective nanocarrier uptake in DCs, both in vitro and in vivo in a mouse model of heart disease. Overall, my work expands on the current applications of PEG-b-PPS nanocarriers, and demonstrates that these nanocarriers can be engineered for diagnostic applications and molecular imaging via stable encapsulation of MRI contrast agents.

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