Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid
- Title
- Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid
- Creator
- Shamjith S.; Murali V.P.; Joesph M.M.; Fathima T.S.; Chandana R.; Jayarajan R.O.; Maiti K.K.
- Description
- The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in always on photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy. 2024 American Chemical Society.
- Source
- ACS Applied Materials and Interfaces, Vol-16, No. 21, pp. 27114-27126.
- Date
- 2024-01-01
- Publisher
- American Chemical Society
- Subject
- activatable PDT; ATP reduction; clinical validation; disrupting glycolysis; enhanced apoptosis; H2S depletion; stimuli-responsive activation
- Coverage
- Shamjith S., Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Kerala, Thiruvananthapuram, 695019, India, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; Murali V.P., Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Kerala, Thiruvananthapuram, 695019, India; Joesph M.M., Department of Life Sciences, Christ University, Bangalore, 560029, India; Fathima T.S., Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Kerala, Thiruvananthapuram, 695019, India; Chandana R., Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Kerala, Thiruvananthapuram, 695019, India, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; Jayarajan R.O., Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Kerala, Thiruvananthapuram, 695019, India, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; Maiti K.K., Chemical Sciences & Technology Division (CSTD), Organic Chemistry Section, CSIR-National Institute for Interdisciplinary Science & Technology (CSIR-NIIST), Industrial Estate, Pappanamcode, Kerala, Thiruvananthapuram, 695019, India, Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
- Rights
- Restricted Access
- Relation
- ISSN: 19448244; PubMed ID: 38747624
- Format
- Online
- Language
- English
- Type
- Article
Collection
Citation
Shamjith S.; Murali V.P.; Joesph M.M.; Fathima T.S.; Chandana R.; Jayarajan R.O.; Maiti K.K., “Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid,” CHRIST (Deemed To Be University) Institutional Repository, accessed February 25, 2025, https://archives.christuniversity.in/items/show/13078.