Photoactivable Platforms for Nitric Oxide Delivery with Fluorescence Imaging

Abstract

The multifaceted role nitric oxide (NO) plays in human physiology and pathophysiology has stimulated a massive interest on NO-releasing compounds for therapeutic purposes. A main issue associated with use of NO donors is the precise spatiotemporal control of the NO release, as its effects are strictly site- and dose-dependent. NO photochemical precursors permit surmounting this difficulty since triggering with light offers an exquisite control of location and timing of NO delivery. On the other hand, the combination of NO photodonors with fluorescent components remains an urgent need for image-guided phototherapeutic treatments based on the use of NO. Fluorescence techniques permit not only an easy tracking of the photoprecursor in a biological environment but also the real-time quantification of the NO photoreleased therein in a non-invasive fashion. In this Focus Review we seek to provide an overview of recent advances in photoactivable platforms developed in our and other laboratories which combine the photoregulated release of NO with fluorescent functionalities. We shall focus attention on NO photoreleasing systems exhibiting 1) persistent fluorescence and 2) photoactivable fluorescence signals, highlighting their logical design and potential developments for phototheranostics.

A Three‐Color Fluorescent Supramolecular Nanoassembly of Phototherapeutics Activable by Two‐Photon Excitation with Near‐Infrared Light

“…Therefore, the delivery of NO by light‐activable NO donors, namely NO photodonors (NOPDs), holds very promising features in cancer research in view of the superb spatiotemporal control that the light offers. Additional control on NO dosage can be achieved by designing NOPDs that possess a fluorescent reporting function . In these cases, a highly fluorescent coproduct released concomitantly to the photorelease of NO acts as an optical counter for this species, offering the possibility to better monitoring the NO release in cells by non‐invasive fluorescence techniques .…”

“…The visualization of PSs and NOPDs in cellular environment through fluorescence techniques represents an indispensable requisite in view of image‐guided phototherapy . In such a way, excitation of the fluorophoric unit with low intensity light generates fluorescence emission, which allows localizing the photoprecursors in cells.…”

A Nonmetal‐Containing Nitric Oxide Donor Activated with Single‐Photon Green Light

“…On the basis of these considerations, and motivated by our ongoing interest in NO photoreleasing systems,, we report herein the novel organic NO photoreleaser, ( Z )‐ 1 , which integrates the spontaneous NO releaser Cupferron and a boron‐dipyrromethene (BODIPY) derivative in the same molecular skeleton (Scheme ). We demonstrate that photoexcitation of the BODIPY light‐harvesting center with green light (530–550 nm) induces heterolytic cleavage of the C−O bond, unmasking Cupferron, which releases NO.…”

Fluorescent Nitric Oxide Photodonors Based on BODIPY and Rhodamine Antennae

“…This has stimulated am assive interest in searchinga nd developing of suitable NO donors for research on the bio-function of NO and on its use as "unconventional" therapeuticsw ith ex-citing prospectsi nh ealthcare including cardiovascular,b acterial and cancerd iseases. [6] In fact, excitation of the NOPD with low intensity light generates fluorescencee mission, which allowsi ts tracking in cells. [4] This has made the NO donors activated by light stimuli, namely NO photodonors (NOPDs), very appealing in view of superb spatiotemporal accuracy that can be achieved by tuningt he site, duration and intensity of the irradiation source.…”