UC Santa Cruz

Theranostic systems are materials or processes that combine modalities of diagnostic imaging with the delivery of therapeutics. The information obtained from theranostic drug-delivery systems can be used to make decisions in real time in efforts to optimize the treatment. This combination of therapy and diagnostics in a single treatment is a viable method for improving drug efficacy, patient safety, and therapeutic outcomes. The theranostic delivery of carbon monoxide (CO) as a chemotherapeutic and silver (Ag+) as an antibacterial agent is discussed in detail in the following chapters.

The gaseous signaling molecule carbon monoxide has been recently recognized for its wide range of physiological activity as well as its antineoplastic properties. Endogenously produced CO directly regulates heme protein activity and indirectly modulates a variety of biochemical processes. Exogenous delivery of CO is also a viable strategy for influencing cellular biochemical responses in efforts to elicit desired salutary therapeutic effects. However, the main technical challenge is the delivery of this noxious and potentially hazardous gas in a controlled and dependable manner.

Several elegant strategies have been designed and implemented for the delivery of this gaseous signaling molecule to cells, including photo-triggered CO releasing systems (molecules, materials, carriers). Light can be used as a benign remote trigger for the on-demand release of CO from photoactivatable CO-releasing systems (photoCORs). However, the delivery of CO to light inaccessible cavities/tissues with spatiotemporal control is a considerable challenge.

The delivery of CO to remote parts of the body through the use of an optical fiber-based CO-releasing device is discussed in Chapter 2.I. The CO-releasing polymeric material described in this chapter can be used as a solid-state source of CO triggered through external light illumination. In addition, this material exhibits a color change upon CO release, indicating qualitatively the extent of CO delivered to cells and therefore has promising in vivo applications. Chapter 2.II describes the use of luminescent rhenium complexes that can also be covalently attached within polymeric matrices for the theranostic remote delivery of CO.

Strategies for tracking photoCORMs within cellular matrices and increasing their internalization are discussed in chapter 3. The cellular penetration rates of photoCORMs with distinct solubilities are investigated through confocal microscopy using a luminescent tag. Chapter 3.II focuses on investigating the luminescence quenching of fluorophores conjugated to a manganese metal center. The use of fluorescent tags allows for the convenient tracking photoCORMs and therefore theranostic delivery of CO to cellular targets in vitro .

Chapter 4 examines the theranostic delivery of silver for antimicrobial chemotherapy. Silver has been used as an antimicrobial agent since ancient times and it continues to be used in a variety of biomedical devices and consumer products. Silver exerts its antimicrobial properties by binding functional groups of amino acids, disrupting biochemical processes. Chapter 4.I discusses two antimicrobial silver complexes that exhibit a luminescence enhancement upon release of Ag+. The increase in luminescence observed can be used to track the extent of Ag+ delivered to microbial cells in vitro. Chapter 4.II describes the incorporation of luminescent silver complexes into a soft agar hydrogel for the treatment of skin and soft tissue infections. In this case, the complexes exhibit a change in luminescence upon silver release. Finally, chapter 4.III discusses the synthesis of a helical dinuclear silver complex and its antimicrobial efficacy in a skin and soft tissue infection model. The luminescence of the tridentate ligand is quenched, similarly to what was observed with the complexes described in chapter 4.I, which can be used to monitor the delivery of Ag+ through “turn on” luminescence.

The theranostic drug-delivery systems described here aim to monitor the delivery of anticancer and antimicrobial therapeutics to cellular targets. This emerging science provides a unique opportunity to tailor and adjust drug-releasing events in real time to achieve the desired therapeutic effects. The change in luminescence in these systems can be extrapolated to determine the extent of drug delivered and/or the amount of prodrug remaining in the delivery system.