UVA-Triggered Drug Release and Photo-Protection of Skin

Abstract

Light has attracted special attention as a stimulus for triggered drug delivery systems (DDS) due to its intrinsic features of being spatially and temporally tunable. Ultraviolet A (UVA) radiation has recently been used as a source of external light stimuli to control the release of drugs using a "switch on- switch off" procedure. This review discusses the promising potential of UVA radiation as the light source of choice for photo-controlled drug release from a range of photo-responsive and photolabile nanostructures via photo-isomerization, photo-cleavage, photo-crosslinking, and photo-induced rearrangement. In addition to its clinical use, we will also provide here an overview of the recent UVA-responsive drug release approaches that are developed for phototherapy and skin photoprotection.

Keywords: UVA-triggered drug release; caged iron chelators; drug delivery systems (DDS); skin photo-protection; smart sunscreens; up-conversion nanoparticles.

Figure 1

Schematic diagram representing the controlled drug release mediated by the UV light-induced changes to molecular structures.

Figure 2

Schematic diagram of the molecular mechanisms by which UVA induces drug release through different mechanisms. (A) Photo-isomerization (Stranius and Börjesson, 2017); (B) Photo-cleavage (Kauscher et al., 2019); (C) Photo-crosslinking (Tunc et al., 2014); (D) Photo-induced rearrangement (Olejniczak et al., 2015). R = aliphatic group.

Figure 3

(A) Photo-isomerization of BHA-liposome (a) Chemical structure and photo-isomerization of BHA; (b) The microstructure schematic of the trans- and cis-BHA-liposome; (c) The UV-visible spectra of BHA-liposomes showing changes upon isomerization; (d) Changes in the absorbance of the BHA-liposome at 348 nm during alternating cycles of UV and visible light; (e) I_II_m values for the BHA-liposome with time upon alternating irradiation with UV and visible light. (B) Drug release from a liposome: (a) Curcumin release from liposomes in the dark (black line) and upon UV irradiation (red line); (b) The accumulated release of curcumin from BHA-curcumin-liposomes upon alternate irradiation by UV and visible light. Reproduced with permission (Liu and An, 2019). Copyright 2018, Elsevier. BHA, 4-butylazobenzene-4-hexyloxy-trimethyl-ammonium trifluoroacetate.

Figure 4

Approach to the analysis of cell membrane delivery and release using copper-free “click” chemistry and a photo-cleavage. (1) Cells are treated with lipid-tethered compound; (2) Cells are treated with “azide fluor 448” to give ‘clicked' compound; (3) Cells are treated with UV light to effect photo-cleavage and release fluorophore (λ_em = 501 nm, λ_ex = 525 nm).

Figure 5

(A) Plot for the potential molecular mechanism of inducing apoptosis with UCNPs@TiO2-based NIR light-mediated PDT treatment. (B) Cell viability after 980 nm laser irradiation for different intensities for 30 min (5 min break after 10 min of irradiation). (C) After UV light irradiation at 365 nm for different irradiation times. (D) In vitro viability of HeLa cells treated with UCNPs@TiO2 NCs. (E) In vitro tumor volume changes of tumor-bearing mice in different groups after various treatments. (F) Digital photograph of excised tumors from representative mice after various treatments. Data for (B–E) are means ± SD, n = 3. Adapted with permission from Hou et al. (2015). Copyright 2015, American Chemical Society.

Figure 6

Schematic diagram of photo-protection by UVA-induced drug release on the skin. (A) Nanoparticles remain on stratum corneum before sun exposure; (B) Nanoparticles release the drug after sun exposure.

Figure 7

The use of mitochondrial targeted tricatechol iron chelator for skin photoprotection. (A) The structure of the chelator (compound 2). (B) Microscopy analysis of the subcellular localization of compound 2 tagged with a fluorescent unit (a) Phase contrast; (b) Compound 2 with the fluorescent unit; (c) Mitochondria stained with mito tracker (d) Merged data. Scale bar = 10 μm; (C) Compound 2 protects FEK4 cells from UVA-induced cell death (a) Bright-field images were captured 24 h after treatment. Swelling (arrow in insert) is indicative of cell death by necrosis and is visible after UVA treatment alone or in the combination of compound 2-Fe. Scale bar = 50 μm; (b) Cells analyzed by flow cytometry. Live cells are defined as Annexin V-negative/PI-negative (lower left-hand quadrant). (D) Compound 2 significantly reduces UVA-induced damage to mitochondria membrane (a) Bar chart of the results of TMRM staining experiment; (b) FEK4 cells were pre-treated with either compound 2 alone or as a complex with iron. Data are means ± SD, n = 3-5. TMRM, tetramethylrhodamine methyl ester; UVA, ultraviolet A. Adapted with permission under the terms of CC BY 4.0 license (Reelfs et al., 2016). Copyright 2016, The Authors. Published by Elsevier.