A New Glutathione-Cleavable Theranostic for Photodynamic Therapy Based on Bacteriochlorin e and Styrylnaphthalimide Derivatives

Abstract

Herein, we report a new conjugate BChl–S–S–NI based on the second-generation photosensitizer bacteriochlorin e6 (BChl) and a 4-styrylnaphthalimide fluorophore (NI), which is cleaved into individual functional fragments in the intracellular medium. The chromophores in the conjugate were cross-linked by click chemistry via a bis(azidoethyl)disulfide bridge which is reductively cleaved by the intracellular enzyme glutathione (GSH). A photophysical investigation of the conjugate in solution by using optical spectroscopy revealed that the energy transfer process is realized with high efficiency in the conjugated system, leading to the quenching of the emission of the fluorophore fragment. It was shown that the conjugate is cleaved by GSH in solution, which eliminates the possibility of energy transfer and restores the fluorescence of 4-styrylnaphthalimide. The photoinduced activity of the conjugate and its imaging properties were investigated on the mouse soft tissue sarcoma cell line S37. Phototoxicity studies in vitro show that the BChl–S–S–NI conjugate has insignificant dark cytotoxicity in the concentration range from 15 to 20,000 nM. At the same time, upon photoexcitation, it exhibits high photoinduced activity.

Photodynamic Therapy: From the Basics to the Current Progress of N-Heterocyclic-Bearing Dyes as Effective Photosensitizers

“…In addition, the fluorescence properties of the fluorophore unit enhance the use of these molecules for theranostics. Other similar studies based on naphtalimide-bearing bacteriochlorins are also reported in recent original articles [ 202 , 204 , 205 ].…”

“…While naturally occurring metal complexes derived from bacteriochlorophylls are unstable and have limited use, there are now synthetic compounds recently described that belong to the bacteriochlorin family and are highly photostable [ 199 , 200 ]. Therefore, two significant issues with bacteriochlorophylls must be addressed for their phototherapeutic application: firstly, they are prone to instability, which can lead to unintended dehydrogenation and subsequently the formation of a chlorin; and secondly, the rigidity of their macrocycle makes it challenging to perform synthetic transformations [ 198 , 201 , 202 ].…”

Light-Deactivated Fluorescent Probes (FLASH-Off) for Multiplexed Imaging

“…36 The challenge was to develop a photo-responsive triazene linker stable enough to withstand spontaneous hydrolysis during synthesis or imaging and function independently in the presence of reducing agents, in contrast to recently reported reductively cleavable photosensitized linkers. 37 We explored the synthesis of multiple triazene analogues and optimized triazene linker 3. Once installed, the linker allowed for further chemical modifications to attach handles for conjugating macromolecules to the fluorochromes.…”

Fluorescent Materials with Excellent Biocompatibility and Their Application in Bio-Sensing, Bio-Imaging

“…Thus, the detection of glutathione has become a critical issue. Prof. Pavlova fabricated a new GSH probe, BChl-S-S-NI, based on the second-generation photosensitizer bacteriochlorin e6 (BChl) and a 4-styrylnaphthalimide fluorophore (NI) [1]. They verified that the energy transfer process of BChl-S-S-NI is realized with high efficiency in the conjugated system, leading to the emissions of the fluorophore fragment being quenched.…”

“…Biocompatibility is the top priority when fluorescent materials are used in bio-fields; a great number of biocompatible fluorescent materials (BFMs) have been obtained, such as organic small-molecule dyes, fluorescent conjugated polymers, metal nanoclusters, rare earth ion-based nanoparticles (e.g., rare-earth-doped upconversion nanoparticles), quantum dots, carbon nanomaterials (e.g., carbon nanotubes and carbon nanodots) and various fluorescent proteins. This Special Issue, "Fluorescent Materials with Excellent Biocompatibility and Their Application in Bio-Sensing, Bio-Imaging", includes twelve research articles covering biosensors based on ion sensors, the detection of pathological oxidative stress and disease detection [1][2][3][4][5][6][7][8][9][10][11][12], as well as four review articles focused on different types of fluorescent probes and biological applications [13][14][15][16].…”