Photoactivatable o-Hydroxycinnamic Platforms for Bioimaging and Therapeutic Release

Abstract

Photoactivatable or photoremovable protecting groups (PPGs) have become a powerful material and gained enormous interest in the field of biomedical applications. PPGs have been utilized for noninvasive, on-demand, spatio-temporal controlled release of biological effectors by irradiation with light to induce biochemical function. Over the past few years, o-hydroxycinnamate (oHC)-based PPGs have received considerable attention for the release of molecules of interest by either UV (one-photon) or near-IR (two-photon) irradiation. In this miniperspective, we have summarized the development of oHC PPGs for bioimaging and the controlled release of therapeutics, bioactive volatiles and other payloads with real-time monitoring. In addition, several future perspectives of oHC systems have been highlighted at the end of this miniperspective.

Visible and NIR light photoactivatableo-hydroxycinnamate system for efficient drug release with fluorescence monitoring

“…In general, the o HC-GMC prodrug undergoes trans -to- cis photoisomerization followed by lactonization to form a fluorescent coumarin product, thereby facilitating the release of GMC . 23,33,37…”

“…In general, the oHC-GMC prodrug undergoes trans-to-cis photoisomerization followed by lactonization to form a fluorescent coumarin product, thereby facilitating the release of GMC. 23,33,37 Next, we determined the uncaging quantum yields of oHC-GMC upon irradiation with visible light. The uncaging quantum yield (Φ u ) of E-to-Z photoisomerization of oHC-GMC after one-photon excitation with visible light was determined to be 0.028 (±0.007%), which is comparable to that of other reported oHC-based systems wherein the photouncaging studies were performed under UV light (Table S1 †).…”

“…The biological activities of such molecules can be restored upon removal of these photoactivatable groups by irradiation with a suitable wavelength of light. To date, various PPGs or PCs have been developed based on o-nitrobenzyl, 7-14 coumarinyl, 5,[7][8][9][10][11][15][16][17] anthracenyl, [7][8][9][10]18,19 quinolinyl, [7][8][9][10]20,21 p-hydroxyphenacyl, 7-10,22 o-hydroxycinnamate, [8][9][10][23][24][25][26][27] rhodamine, 10,28 cyanine, 8,10,11,29 BODIPY, 8,10,11,30 etc. These compounds are successfully used for non-invasive spatiotemporal control over the release of biologically important compounds such as anticancer agents, antibiotics, biomolecules, neurotransmitters, fragrances, fluorescent probes, etc.…”

“…However, most of these PPGs or PCs require high-energy UV light for their removal, which limits their biological and medical applications, since UV light is harmful to biomatter and has a quite narrow penetration potential in human tissues. 8,10,16,23 Therefore, the development of new PPGs that can be efficiently activated by biologically and chemically benign visible and near-infrared (NIR) light is highly desired to achieve deeper tissue penetration and to diminish phototoxicity.…”

“…In recent years, o-hydroxycinnamate (oHC)-based photocaged systems have received ample attention because of their (i) ease of synthesis, (ii) clean and rapid photouncaging capability, (iii) applicability for two-photon uncaging efficiencies by NIR light irradiation, (iv) facile conjugation with alcohols and amines without forming a carbonate bond, which is highly labile in physiological conditions, and (v) resulting photoproduct coumarin derivatives which are strongly fluorescent that served as a fluorescent reporter for the real-time monitoring of the release of substrates. 23,26 The photo-uncaging capabilities of the oHC systems were first described by Porter et al to accomplish photochemical activation of serine proteinase enzymes. 24,31,32 Jullien et al have utilized the phototriggering ability of oHC for the release of caged substrates such as alcohol in real-time by monitoring the formation of fluorescent coumarin reporter by irradiation with two-photon light.…”