Universal Scaffold for an Activatable Photosensitizer with Completely Inhibited Photosensitivity

Abstract

Activatable photosensitizers (aPSs) sensitive to specific stimuli hold potential for targeting multiple disease biomarkers and are desirable for photodynamic therapy (PDT). Presented herein is the design of aPSs that can be activated and fully recover from an inhibited state in the presence of specific biomarker. A designed long‐wavelength D‐π‐A photosensitizer, PSSe‐I, with highly efficient photosensitivity for generation of 1O2 was used. Caging of the phenolate donor of PSSe‐I with a biomarker‐sensitive group provided ALPPS, and the drastic activation of its photosensitivity was demonstrated intracellularly. To enhance the flexibility of the design strategy, a clickable azide group was introduced into the scaffold to allow integration of more functionality. Modularly derived mito‐PNPS, equipped with a mitochondria‐targeting group and a specific peroxynitrite‐reactive trigger, was synthesized and demonstrated superior performance in cells. This strategy could lead to customization of aPSs applicable to a specific PDT.

In‐vitro and In‐vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts

“…As an on-invasive cancer therapeutic technique,p hototherapy provides spatiotemporal control over drug activation, overcoming the problems of chemotherapeutic drugs such as severe side effects and acquired drug resistance. [1][2][3][4] Traditionally,p hototherapy uses light activation of an organic photosensitizer (PS) to react with tissue oxygen for the generation of highly cytotoxic singlet oxygen ( 1 O 2 )via atype II mechanism. [1][2][3][4] However,afew factors such as low aqueous solubility and oxygen dependent mechanism of action limit their application.…”

“…[1][2][3][4] Traditionally,p hototherapy uses light activation of an organic photosensitizer (PS) to react with tissue oxygen for the generation of highly cytotoxic singlet oxygen ( 1 O 2 )via atype II mechanism. [1][2][3][4] However,afew factors such as low aqueous solubility and oxygen dependent mechanism of action limit their application. [3,4] To overcome the limitations of organic PSs,p hotoactive metal complexes are under investigation as next generation PSs for phototherapy.…”

A Glutathione Activatable Photosensitizer for Combined Photodynamic and Gas Therapy under Red Light Irradiation

“…The design of so called "activable photosensitizers" can solve the aforementioned problem. [14][15][16] Photosensitizers functionalized with caged groups are initially inactive and their activity could be triggered by conditions specific to the tumor microenvironment including intracellular hypoxia, lysosome acidic environment, or overexpressed glutathione (GSH) and enzymes. [17,18] Therefore, the design of activable photosensitizers is of great importance for precise PDT with minimizing the side effects to healthy tissues.…”

A Photosensitive Polymeric Carrier with a Renewable Singlet Oxygen Reservoir Regulated by Two NIR Beams for Enhanced Antitumor Phototherapy

“…Intense green fluorescence of the oxidized DCF was observed (Figure 5b i), indicating the effective 1 O 2 generation during the laser-1-induced PDT process. On the contrary, HeLa cells pretreated with sodium azide (NaN 3 ; 1 O 2 scavenger [70] ) displayed undetectable fluorescence upon laser-1 irradiation, further verifying the photosensitized 1 O 2 generation of An-NP (Figure 5c and Figure S17, Supporting Information). In group 2, the cells were incubated with EPO-NP (for its preparation, see the Supporting Information) and DCF-DA, then subjected to laser-2 irradiation (1.0 W cm −2 ) or incubated in dark for 10 min before imaging.…”