Nanocarriers for nitric oxide delivery

Abstract

Nitric oxide (NO) is a promising pharmaceutical agent that has vasodilative, antibacterial, and tumoricidal effects. To study the complex and wide-ranging roles of NO and to facilitate its therapeutic use, a great number of synthetic compounds (e.g., nitrosothiols, nitrosohydroxyamines, N-diazeniumdiolates, and nitrosyl metal complexes) have been developed to chemically stabilize and release NO in a controlled manner. Although NO is currently being exploited in many biomedical applications, its use is limited by several factors, including a short half-life, instability during storage, and potential toxicity. Additionally, efficient methods of both localized and systemic in vivo delivery and dose control are needed. One strategy for addressing these limitations and thus increasing the utility of NO donors is based on nanotechnology.

Figure 1

Scanning electron micrograph of polymeric nanoparticles containing the NO donor agent trans-[RuCl([15]ane)(NO)]²⁺. (a) Panoramic view. (b) Isolated magnified particle. Reprinted from Oliveira et al. [6], with the permission of Editorial Executive, Research Trends.

Figure 2

Generation-4 PAMAM with a completely modified exterior (64 thiols) of S-nitroso-N-acetyl-D,L-penicillamine (G4-SNAP) or S-nitroso-N-acetylcysteine (G4-NACysNO). Reprinted from Stasko et al. [76], with the permission of American Chemical Society, ACS Publications.

Figure 3

Structure of a OSM-PCLA-PEG-PCLA-OSM hydrogel. Reprinted from Nguyen and Lee [77], with the permission of Copyright and Licensing Manager, Wiley-VCH Verlag GmbH & Co.

Figure 4

Schematic representation of the stabilization of zwitterionic diazeniumdiolate by loading liposomes. Reprinted from Tai et al. [89], with the permission of Elsevier.

Figure 5

Nanocontainers for NO storage. Reprinted from Ghosh et al. [116], with the permission of Elsevier.

Figure 6

Schematic representation of the synthesis of N-diazeniumdiolate-modified SiNPs using TEOS and N-(6-aminohexyl)aminopropyltrimethoxysilane as tetraalkoxysilane and aminoalkoxysilane precursors. Reprinted from Seabra and Durán [31], with the permission of Royal Society of Chemistry (http://www.rsc.org).

Figure 7

In vivo targeting and imaging using QDs. (a) Ex vivo tissue examination of QD-labeled cancer cells trapped in a mouse lung [129]. (b) Near-infrared fluorescence of water-soluble type II QDs taken up by sentinel lymph nodes [130]. (c) In vivo simultaneous imaging of multicolor QD-encoded microbeads injected into a live mouse [131]. (d) Molecular targeting and in vivo imaging of a prostate tumor in a mouse using a QD-antibody conjugate (red) [131]. Reprinted from Gao et al. [128], with the permission of Elsevier.

Figure 8

Size-dependent optical effects of semiconductor nanoparticles. Semiconductor nanoparticles contain size-dependent electronic and optical properties. A series of five different emission spectra of sized ZnS-capped CdSe nanoparticles called QDs is used to demonstrate this principle (colored dotted lines), in juxtaposition with the absorption spectrum (solid black line).