Emissive polymer vesicles: Soft nanoscale probes for in vivo optical imaging.

摘要

Situated at the interface between the basic and applied life sciences, molecular imaging is a rapidly expanding field that focuses upon the study of molecular interactions in the context of live organisms. Interdisciplinary investigations aim to elucidate dynamic multi-factorial processes that underlie physiological and diseased states, impacting not only our fundamental understanding of nature, but also pharmaceutical drug development, medical diagnosis, patient-specific therapy, and post-treatment monitoring. Magnetic resonance, nuclear, and optical imaging modalities are the most useful for molecular-level investigations. In particular, optical imaging has distinct advantages in small animal research due to its superior availability (time, cost, and user experience), quantitative sensitivity, and safety (reliance on non-ionizing radiation). Clinical translation of novel optical technologies, however, is incumbent upon the continued evolution of chemical probes that bind to specific biological targets and produce energetic signals from within the body. While significant progress has been made in constructing target-specific and locally active near-infrared-emissive fluorophores (NIRFs), the development of biodegradable contrast agents of appropriate sensitivity remains a major technological hurdle for the realization of deep-tissue fluorescence-based imaging.; The focus of this thesis dissertation is upon the design and development of the first-generation of biodegradable, nanoscale optical probes capable of high-intensity emission through clinically relevant tissue depths (several centimeters). The studies described herein focus upon a class of porphyrin-based supermolecular fluorophores that possess ideal properties for biomedical imaging. Their large size and hydrophobic nature, however, underscore their need for an appropriate amphipathic delivery vehicle to facilitate their successful in vivo application. When compared to natural nanoscale carriers such as liposomes and low-density lipoprotein, or synthetic vehicles including dendrimers, micelles, and solid nanoparticles, polymersomes (vesicles comprised of amphiphilic block copolymers) hold distinct advantages for the stable incorporation and delivery of porphyrinic NIRFs. Through fundamental biophysical, spectroscopic, and imaging studies, optimization of emissive polymersome optical, physical, and biomaterial properties is undertaken with respect to their ultimate in vivo utility.