Cu(ii)-BODIPY photosensitizer for CAIX overexpressed cancer stem cell therapy.
Hyo Sung JungSeyoung KooMiae WonSeeun AnHaebeen ParkJonathan L SesslerJiyou HanJong Seung KimPublished in: Chemical science (2023)
Chemoresistance originating from cancer stem cells (CSCs) is a major cause of cancer treatment failure and highlights the need to develop CSC-targeting therapies. Although enormous progress in both photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been made in recent decades, the efficacy of these modalities against CSC remains limited. Here, we report a new generation photosensitizer, CA9-BPS-Cu(ii), a system that combines three subunits within a single molecule, namely a copper catalyst for CDT, a boron dipyrromethene photosensitizer for PDT, and acetazolamide for CSC targeting via carbonic anhydrase-9 (CA9) binding. A therapeutic effect in MDA-MB-231 cells was observed that is ascribed to elevated oxidative stress mediated by a combined CDT/PDT effect, as well as through copper-catalysed glutathione oxidation. The CSC targeting ability of CA9-BPS-Cu(ii) was evident from the enhanced affinity of CA9-BPS-Cu(ii) towards CD133-positive MDA-MB-231 cells where CA9 is overexpressed vs. CD133-negative cells. Moreover, the efficacy of CA9-BPS-Cu(ii) was successfully demonstrated in a xenograft mouse tumour model.
Keyphrases
- photodynamic therapy
- induced apoptosis
- cell cycle arrest
- cell therapy
- single molecule
- fluorescence imaging
- oxidative stress
- cancer stem cells
- protein kinase
- metal organic framework
- endoplasmic reticulum stress
- cell death
- signaling pathway
- aqueous solution
- mesenchymal stem cells
- nitric oxide
- squamous cell carcinoma
- atomic force microscopy
- breast cancer cells
- cell proliferation
- pi k akt
- gold nanoparticles
- ionic liquid
- carbon dioxide
- squamous cell