Intracellular Modulation of Excited‐State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells

Abstract

The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O 2 (a 1 D g )], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer-related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH). The reaction alters the properties of both the ground and excited states, consequently enabling the efficient generation of singlet oxygen. Remarkably, the designed photosensitizer can discriminate between different concentrations of GSH in normal and cancer cells and thus remains inefficient as a photosensitizer inside a normal cell while being transformed into a lethal singlet oxygen source in cancer cells. This is the first demonstration of such a difference in the intracellular activity of a photosensitizer.

A Three‐Component Assembly Promoted by Boronic Acids Delivers a Modular Fluorophore Platform (BASHY Dyes)

“…The quest for flexible and modular approaches that enablet he construction of electronically tunablea nd environmentally responsivef luorophore platformsi sv ital for the development of functional dyes for bioimaging, sensing, and probinga pplications. [1][2][3][4][5] Highly fluorescent dyes based, for example, on rhodamine, [6,7] fluorescein, [3,8] oxazine, [3] coumarin, [3] cyanine [9,10] or boron dipyrromethene (BODIPY) [11][12][13][14][15] chromophores, have been extensively explored along these lines. In particular, BODIPY derivatives (Scheme 1A)b ecame the focus of different fields due to ac ombination of remarkable photophysical properties,w hich included very high quantum yields, narrow absorptiona nd emission bands, and high molar absorption coefficients.…”

Recent Advances in Activatable Organic Photosensitizers for Specific Photodynamic Therapy

“…[34] Based on the principle of tuning electronical similarity, Akkaya et al designed a GSH-responsive dissymmetric dimeric BODIPY dye (DiBDP, i. e. compound 5) with low ISC efficiency and suppressed photosensitivity due to non-DS-TR property (Fig-ure 5). [35] After treatment with thiol, the styryl double bond was saturated to electrically isolate the pendent methylpyridinium (MP) substituent. The resulting product (DiBDPÀ S, i. e. compound 5 m) gained the required similarity for DS-TR state and therefore restore the strong photosensitivity.…”

Superior Photodynamic Therapy of Colon Cancer Cells by Selenophene‐BODIPY‐Loaded Superparamagnetic Iron Oxide Nanoparticles

“…Hydrophilic groups such as sulfonyl groups or polyethylene glycolic units have been implemented to the core structure to improve the water solubility, however, in most cases these modifications require lengthy and complicated synthetic pathways and restrict the design flexibility [31,32] . On the other side, modulation of excited state dynamics of BODIPY‐based PSs by photo‐induced electron (PeT), intramolecular charge transfer (ICT) or energy transfer mechanisms have been widely utilized to enhance the tumor selectivity as these processes and inter‐system crossing (ISC) are competing with each other [33–36] . However, this design principle cannot eliminate cytotoxicity on healthy cells in most cases.…”

“…[31,32] On the other side, modulation of excited state dynamics of BODIPY-based PSs by photo-induced electron (PeT), intramolecular charge transfer (ICT) or energy transfer mechanisms have been widely utilized to enhance the tumor selectivity as these processes and intersystem crossing (ISC) are competing with each other. [33][34][35][36] However, this design principle cannot eliminate cytotoxicity on healthy cells in most cases.…”