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

Abstract

Although photodynamic therapy (PDT) is a promising approach for cancer therapy, most existing photosensitizers lack selectivity for tumor cells and the overexpressed glutathione (GSH) in tumor cells reduces the PDT efficiency. Therefore, designing photosensitizers that can be selectively activated within tumor cells and combine PDT with other therapeutic modalities represents a route for precise and efficient anticancer treatment. Herein, an organic activatable photosensitizer, CyI-DNBS, bearing 2,4-dinitrobenzenesulfonate (DNBS) as the cage group is reported. CyI-DNBS can be uptaken by cancer cells after which the cage group is selectively removed by the intracellular GSH, resulting in the generation of SO 2 for gas therapy. The reaction also releases the activated photosensitizer, CyI-OH, that can produce singlet oxygen ( 1 O 2 ) under red light irradiation. Therefore, CyI-DNBS targets cancer cells for both photodynamic and SO 2 gas therapy treatments. The activatable photosensitizer provides a new approach for PDT and SO 2 gas synergistic therapy and demonstrates excellent anticancer effect in vivo.

A Two‐In‐One Nanoprodrug for Photoacoustic Imaging‐Guided Enhanced Sonodynamic Therapy

“…As shown in Figure 1G, the test paper lightened when exposed to the mixture of P-DOA NPs and Cys in a time-and concentration-dependent manner, indicating that P-DOA NPs can react with thiols to produce SO 2 . [38,43] In addition to the release of SO 2 , the reaction of DOA with thiol molecules (GSH or Cys) will also generate ALA (Scheme S2, Supporting Information). Thus, the release behavior of ALA from P-DOA NPs was then tested.…”

Fluorescent Self-Reporting Lipid Nanoparticles for Nitric Oxide/Gene Co-Delivery and Combination Therapy

“…Cancer is currently one of the most common causes of death worldwide. To effectively treat cancer, researchers have tried a variety of treatments including gene therapy, − chemotherapy, , radiotherapy, , and gas therapy. − As an emerging treatment, gas therapy uses gas transmitters to induce tumor cell death. Studies have found that several gas molecules, such as nitric oxide (NO), carbon monoxide (CO), oxygen (O 2 ), and hydrogen sulfide (H 2 S), could regulate the process of cancer. − Among them, NO was the first found gaseous biochemical messenger, and it played a dual role in tumor progression: low concentrations of NO might promote tumor growth, while high concentrations of NO (>1 μM) could induce tumor cell apoptosis through multiple pathways .…”

Multifunctional Nanosystems Powered Photodynamic Immunotherapy

“…Previous research suggests that photothermal-mediated heating will increase the blood flow and combination with photothermal therapy is regarded to enhance PDT inhibition of hypoxic tumors ( Wu et al, 2019a ; Chen et al, 2022 ). Benefiting from the unique characteristics of multifunctional nanomaterials, multiple therapeutic strategies can be simultaneously mediated by one nanoplatform to synergistically inhibit tumor, such as the combination of gas therapy ( Wan et al, 2018 ; Wang et al, 2022b ) and chemotherapy ( Yang et al, 2019a ; Wang et al, 2019e ), etc., Recently, some emerging nanomaterials such as heterojunction-based nanoparticles have been prepared to enhance the generation efficacy of ROS through catalytic reaction, deriving a new therapeutic strategy termed catalytic therapy. The combination of PDT and catalytic therapy implied a promising strategy to strengthen the therapeutic efficiency ( Pan et al, 2019 ; Kang et al, 2021 ; Kong et al, 2021 ; Pan et al, 2022 ).…”