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Review
. 2014 Aug 10;21(5):730-54.
doi: 10.1089/ars.2013.5754. Epub 2014 Apr 15.

Exploiting oxidative microenvironments in the body as triggers for drug delivery systems

Shivanjali Joshi-Barr  1 , Caroline de Gracia Lux, Enas Mahmoud, Adah Almutairi
Affiliations
Review

Exploiting oxidative microenvironments in the body as triggers for drug delivery systems

Shivanjali Joshi-Barr et al. Antioxid Redox Signal. .

Abstract

Significance: Reactive oxygen species and reactive nitrogen species (ROS/RNS) play an important role in cell signaling pathways. However, the increased production of these species may disrupt cellular homeostasis, giving rise to pathological conditions. Biomaterials that are responsive to ROS/RNS can be strategically used to specifically release therapeutics and diagnostic agents to regions undergoing oxidative stress.

Recent advances: Many nanocarriers intended to exploit redox micro-environments as triggers for drug release, summarized and compared in this review, have recently been developed. We describe these carriers' chemical structures, strategies for payload protection and oxidation-selective release, and ROS/RNS sensitivity as tested in initial studies.

Critical issues: ROS/RNS are unstable, so reliable measures of their concentrations in various conditions are scarce. Combined with the dearth of materials shown to respond to physiologically relevant levels of ROS/RNS, evaluations of their true sensitivity are difficult.

Future directions: Oxidation-responsive nanocarriers developed thus far show tremendous potential for applicability in vivo; however, the sensitivity of these chemistries needs to be fine tuned to enable responses to physiological levels of ROS and RNS.

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Figures

<b>FIG. 1.</b>
FIG. 1.
Chemical structures of aryl boronic ester-based oxidation-responsive systems and corresponding release mechanisms: modified dextran (a), modified polycresol (b). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 2.</b>
FIG. 2.
Chemical structures of ferrocene-based oxidation-responsive systems and corresponding release mechanisms: supramolecular hydrogel based on host-guest inclusion complex (a), nanocapsules containing Fc patches (b). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 3.</b>
FIG. 3.
Chemical structure of proline-based oxidation-responsive system and corresponding release mechanism of a supramolecular hydrogel utilizing a PEG-oligo-proline cross-linker. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 4.</b>
FIG. 4.
Chemical structure of selenium-based oxidation-responsive systems and corresponding release mechanisms: noncovalently connected polymeric superamphiphiles (a), main chain monoselenide and diselenide polymers (b–d), and side-chain selenium-containing polymer (e). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 4.</b>
FIG. 4.
Chemical structure of selenium-based oxidation-responsive systems and corresponding release mechanisms: noncovalently connected polymeric superamphiphiles (a), main chain monoselenide and diselenide polymers (b–d), and side-chain selenium-containing polymer (e). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 5.</b>
FIG. 5.
Chemical structure of thioether-based oxidation-responsive systems and corresponding release mechanisms: thioether (a–d), thioketal (e), and thioether-ketal (f). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 5.</b>
FIG. 5.
Chemical structure of thioether-based oxidation-responsive systems and corresponding release mechanisms: thioether (a–d), thioketal (e), and thioether-ketal (f). To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
<b>FIG. 6.</b>
FIG. 6.
Reactive oxygen species-responsive nanocarriers that release payload in response to redox changes in the microenvironment have tremendous potential as diagnostic and therapeutic agents for a variety of pathophysiological conditions. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars
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