Samuel A. Wickline

Emerging nanomedicine opportunities with perfluorocarbon nanoparticles.

Perfluorocarbon (PFC) nanoparticles can serve as a platform technology for molecular imaging and targeted drug-delivery applications. These nanoparticles are approximately 250 nm in diameter and are encapsulated in a phospholipid shell, which provides an ideal surface for the incorporation of targeting ligands, imaging agents and drugs. For molecular imaging, PFC nanoparticles can carry very large payloads of gadolinium to detect pathological biomarkers with magnetic resonance imaging. A variety of different epitopes, including αvβ3-integrin, tissue factor and fibrin, have been imaged using nanoparticles formulated with appropriate antibodies or peptidomimentics as targeting ligands. Lipophilic drugs can also be incorporated into the outer lipid shell of nanoparticles for targeted delivery. Upon binding to the target cell, the drug is exchanged from the particle surfactant monolayer to the cell membrane through a novel process called ‘contact facilitated drug delivery’. By combining targeted molecular imaging and localized drug delivery, PFC nanoparticles provide diagnosis and therapy with a single agent.

Perfluorocarbon Nanoparticles for Molecular Imaging and Targeted Therapeutics

Molecular imaging is a novel tool that has allowed noninvasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. Until recently, this technique was confined to the field of nuclear imaging; however, advances in nanotechnology have extended this research to include magnetic resonance (MR) imaging, positron emission tomography (PET), single photon emission computed tomography (SPECT), and ultrasound (US), among others. The application of nanotechnology to MR, SPECT, and US molecular imaging has generated several candidate contrast agents. We discuss the application of one multimodality platform, a targeted perfluorocarbon nanoparticle. Our results show that it is useful for noninvasive detection with all three imaging modalities and may additionally be used for local drug delivery.

Molecular MR Imaging with Paramagnetic Perfluorocarbon Nanoparticles

Targeted contrast agents, such as perfluorocarbon (PFC) nanoparticles, have been developed to allow conventional imaging modalities, including MRI, to detect and characterize specific pathological biomarkers of early disease rather than simply observe the anatomical manifestations occurring at very late stages. PFC nanoparticles are typically 200–300 nm in diameter and are encapsulated in a phospholipid shell, which provides an ideal surface for the incorporation of targeting ligands and/or imaging agents. Through chemical modification of the paramagnetic chelates incorporated on the particle surface, nanoparticle relaxivity as well as stability can be increased to improve the efficacy of MR molecular imaging. PFC nanoparticles can be targeted to a number of different biological epitopes, including fibrin, an abundant marker of ruptured atherosclerotic plaques; αvβ3-integrin, an endothelial biomarker of angiogenesis associated with atherosclerosis, tumor growth, and vascular injury; collagen III, a component of the extracellular matrix that is exposed after balloon angioplasty; and tissue factor, a vascular smooth muscle cell (VSMC) marker that is overexpressed following vascular injury. In addition to paramagnetic nanoparticles for 1H MRI, the PFC core has a high fluorine content that can be detected with 19F MRI, providing unambiguous and quantitative mapping of the contrast agent distribution. Another distinctive advantage of PFC nanoparticles for molecular imaging applications is their compatibility with several imaging modalities, including MRI, ultrasound, nuclear imaging, and CT.