Exploiting the Cellular Redox‐Control System for Activatable Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) has been successfully used to treat a variety of cancers. However, one drawback has been the adverse side effects experienced by patients during therapy, as a result of the destruction of normal tissues upon irradiation. Herein, we describe the design, synthesis and characterisation of a photosensitiser to overcome this issue that, in addition to light, is also dependent on the overactive redox system present in cancer cells for its activation. Our probe consists of the photosensitiser, protoporphyrin IX, and a FRET‐based quencher dye, BHQ‐3, on a scaffold containing a disulfide bond. The close proximity of BHQ‐3 to protoporphyrin IX quenches its ability to fluoresce and produce reactive oxygen species, whereas nonenzymatic or enzymatic reduction can recover its native properties. We further demonstrate its ability to be activated in cancer cells in a thiol‐dependent manner and destroy breast and lung cancer cells upon red‐light irradiation.

Changes in Ecophysiology, Osmolytes, and Secondary Metabolites of the Medicinal Plants of Mentha piperita and Catharanthus roseus Subjected to Drought and Heat Stress

“…In contrast to our results, Gharibi et al [69] recently demonstrated increased accumulation of flavonoids and expression of flavonoid biosynthesis genes in Achillea pachycephala after prolonged exposure to drought; the overall effect enhanced oxidative stress due to the increased accumulation of ROS like H 2 O 2 . Under stress conditions, the accumulation of secondary metabolites helps plants to modulate their response mechanisms as these substances act as key signaling components [71,72].…”

“…These metabolites have remarkable biological activities and are often exploited as medicinal and food ingredients for therapeutic, aromatic, and culinary purposes [68]. Increased accumulation of secondary metabolites prevents the oxidative effects of drought stress on the membrane structure and imparts greater pharmacological properties to plants [69]. Drought stress influences the accumulation of key secondary metabolites, including phenols and flavonoids, in Amaranthus [70].…”

Photodynamic Therapy—Current Limitations and Novel Approaches

“…Possible side effects after PDT treatment include skin lesions and the ocular adverse events ( Vrouenraets et al, 2003 ; Huang, 2005 ). In order to improve patient prognosis and enhance PDT response, activatable photosensitizers have been developed ( Li et al, 2017c ; Gharibi et al, 2019 ; Digby et al, 2020 ; Liu and Li, 2020 ; Sun et al, 2020 ; Yuan et al, 2020 ; Zheng et al, 2020 ). The activatable photosensitizer designs can be used as an “ON/OFF” switch controlling PDT for effective cytotoxic singlet oxygen generation in the tumor tissue in vivo .…”

An Activatable Photosensitizer Targeting Human NAD(P)H: Quinone Oxidoreductase 1

“…Lastly, theranostic prodrugs providing both real‐time hNQO1 activity monitoring and anticancer drug release in a single molecule have also been reported . However, despite the diverse set of probes currently exploiting hNQO1, to date, there are no reports of an hNQO1‐targeted optical therapeutic that can be used for PDT . With this in mind, we sought out to develop the first activatable PS (aPS) targeting hNQO1.…”

“…[31,32] However,d espite the diverse seto fp robesc urrently exploitingh NQO1, to date, there are no reportso fa nh NQO1targeted optical therapeutic that can be used for PDT. [33][34][35][36][37][38] With this in mind, we sought out to develop the first activatable PS (aPS)t argeting hNQO1.…”