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BODIPY-Based Photothermal Agents with Excellent Phototoxic Indices for Cancer Treatment


Schneider, Lukas; Kalt, Martina; Koch, Samuel; Sithamparanathan, Shanmugi; Villiger, Veronika; Mattiat, Johann; Kradolfer, Flavia; Slyshkina, Ekaterina; Luber, Sandra; Bonmarin, Mathias; Maake, Caroline; Spingler, Bernhard (2023). BODIPY-Based Photothermal Agents with Excellent Phototoxic Indices for Cancer Treatment. Journal of the American Chemical Society, 145(8):4534-4544.

Abstract

Here, we report six novel, easily accessible BODIPY-based agents for cancer treatment. In contrast to established photodynamic therapy (PDT) agents, these BODIPY-based compounds show additional photothermal activity and their cytotoxicity is not dependent on the generation of reactive oxygen species (ROS). The agents show high photocytotoxicity upon irradiation with light and low dark toxicity in different cancer cell lines in 2D culture as well as in 3D multicellular tumor spheroids (MCTSs). The ratio of dark to light toxicity (phototoxic index, PI) of these agents reaches striking values exceeding 830,000 after irradiation with energetically low doses of light at 630 nm. The oxygen-dependent mechanism of action (MOA) of established photosensitizers (PSs) hampers effective clinical deployment of these agents. Under hypoxic conditions (0.2% O2), which are known to limit the efficiency of conventional PSs in solid tumors, photocytotoxicity was induced at the same concentration levels, indicating an oxygen-independent photothermal MOA. With a PI exceeding 360,000 under hypoxic conditions, both PI values are the highest reported to date. We anticipate that small molecule agents with a photothermal MOA, such as the BODIPY-based compounds reported in this work, may overcome this barrier and provide a new avenue to cancer therapy.

Abstract

Here, we report six novel, easily accessible BODIPY-based agents for cancer treatment. In contrast to established photodynamic therapy (PDT) agents, these BODIPY-based compounds show additional photothermal activity and their cytotoxicity is not dependent on the generation of reactive oxygen species (ROS). The agents show high photocytotoxicity upon irradiation with light and low dark toxicity in different cancer cell lines in 2D culture as well as in 3D multicellular tumor spheroids (MCTSs). The ratio of dark to light toxicity (phototoxic index, PI) of these agents reaches striking values exceeding 830,000 after irradiation with energetically low doses of light at 630 nm. The oxygen-dependent mechanism of action (MOA) of established photosensitizers (PSs) hampers effective clinical deployment of these agents. Under hypoxic conditions (0.2% O2), which are known to limit the efficiency of conventional PSs in solid tumors, photocytotoxicity was induced at the same concentration levels, indicating an oxygen-independent photothermal MOA. With a PI exceeding 360,000 under hypoxic conditions, both PI values are the highest reported to date. We anticipate that small molecule agents with a photothermal MOA, such as the BODIPY-based compounds reported in this work, may overcome this barrier and provide a new avenue to cancer therapy.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Scopus Subject Areas:Physical Sciences > Catalysis
Physical Sciences > General Chemistry
Life Sciences > Biochemistry
Physical Sciences > Colloid and Surface Chemistry
Uncontrolled Keywords:Colloid and Surface Chemistry, Biochemistry, General Chemistry, Catalysis
Language:English
Date:1 March 2023
Deposited On:16 Mar 2023 09:04
Last Modified:30 Mar 2024 02:34
Publisher:American Chemical Society (ACS)
ISSN:0002-7863
OA Status:Green
Publisher DOI:https://doi.org/10.1021/jacs.2c11650
PubMed ID:36780327
Project Information:
  • : FunderUniversität Zürich
  • : Grant IDFK- 085-19
  • : Project Title
  • : FunderColbianco Stiftung
  • : Grant ID
  • : Project Title
  • : FunderSchweizerischer Nationalfonds
  • : Grant ID206021_164018
  • : Project Title
  • Content: Accepted Version
  • Language: English