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| Main Authors: | , , , , , , , |
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| Format: | Artículo Open Access |
| Published: |
Wiley
2025
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| Subjects: | |
| Online Access: | https://onlinelibrary.wiley.com/doi/10.1111/php.70049 |
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Table of Contents:
- Nanoengineered photosensitizers for photodynamic priming to overcome P‐glycoprotein‐mediated multidrug resistance Idrisa Rahman Anju Meda Kaitlyn A. Moore Payal Srivastava Anika Dasgupta Andaleeb Sajid Suresh V. Ambudkar Huang‐Chiao Huang Photochemistry and Photobiology Abstract P‐glycoprotein (P‐gp, ABCB1)‐mediated multidrug resistance (MDR) remains a significant barrier to successful chemotherapy outcomes for cancer patients. While photoactivation of verteporfin (VP), a photosensitizer, has demonstrated success for overcoming MDR through direct protein aggregation upon photoactivation and through adenosine triphosphate (ATP) depletion, the impact of VP's formulation on P‐gp function and cellular energetics has not been fully characterized in this context. In this study, we screened four well‐established VP formulations—liposomal VP (L‐VP), lysophosphatidylcholine‐conjugated VP (lysoPC VP), liposomal formulation of lysoPC VP (L‐lysoPC VP), and a self‐assembled VP nanoaggregate (NanoVP), with a free form of VP as a control—for their ability to inhibit P‐gp. Using a combination of in vitro intracellular VP accumulation assays, P‐gp substrate retention experiments, and Seahorse‐based metabolic profiling, we identified NanoVP as the lead formulation for P‐gp modulation in cancer cells. NanoVP effectively depleted ATP in drug‐resistant cancer cells, while being recognized as a P‐gp substrate. Photodynamic priming with NanoVP at sub‐cytotoxic light doses enhanced P‐gp substrate retention within the cells without damaging P‐gp protein, indicating ATP depletion as the primary mode of functional inhibition. These findings highlighted NanoVP's clinical potential to enhance chemotherapeutic efficacy via photoactivation‐based modulation of P‐gp's function in multidrug‐resistant cancers. 10.1111/php.70049 http://creativecommons.org/licenses/by/4.0/