Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Artículo Open Access |
| Published: |
Wiley
2024
|
| Subjects: | |
| Online Access: | https://onlinelibrary.wiley.com/doi/10.1111/php.13982 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1867003862812983296 |
|---|---|
| author | Soniya Kumbham Kazi Md Mahabubur Rahman Caroline Bosmajian Ganesh Bist Barbara A. Foster Sukyung Woo Youngjae You |
| author_facet | Soniya Kumbham Kazi Md Mahabubur Rahman Caroline Bosmajian Ganesh Bist Barbara A. Foster Sukyung Woo Youngjae You Soniya Kumbham Kazi Md Mahabubur Rahman Caroline Bosmajian Ganesh Bist Barbara A. Foster Sukyung Woo Youngjae You |
| collection | Wiley Open Access |
| contents | Enhancing PDT efficacy in NMIBC: Efflux inhibitor mediated improvement of PpIX levels and efficacy of the combination of PpIX‐PDT and SO‐cleavable prodrugs Soniya Kumbham Kazi Md Mahabubur Rahman Caroline Bosmajian Ganesh Bist Barbara A. Foster Sukyung Woo Youngjae You Photochemistry and Photobiology AbstractProtoporphyrin IX (PpIX)‐based photodynamic therapy (PDT) has shown limited efficacy in nonmuscle‐invasive bladder cancer (NMIBC). To improve PDT efficacy, we developed singlet oxygen‐cleavable prodrugs. These prodrugs, when combined with PpIX‐PDT, induce cancer cell death through both PDT and drug release mechanisms. Inhibition of PpIX efflux was reported to be an effective strategy to improve PpIX‐PDT in certain cancer cells. Our main goal was to investigate whether adding an efflux inhibitor to the combination of PpIX and prodrugs can improve the PpIX levels in bladder cancer cells and the release of active drugs, thus improving the overall efficacy of the treatment. We treated bladder cancer cell lines with lapatinib and evaluated intracellular PpIX fluorescence, finding significantly increased accumulation. Combining lapatinib with prodrugs led to significantly reduced cell viability compared to prodrugs or PpIX‐PDT alone. The effect of lapatinib depended on the expression level of the efflux pump in bladder cancer cells. Interestingly, lapatinib increased paclitaxel (PTX) prodrug uptake by threefold compared to prodrug alone. Adding an efflux inhibitor (e.g., lapatinib) into bladder instillation solutions could be a straightforward and effective strategy for NMIBC treatment, particularly in tumors expressing efflux pumps, with the potential for clinical translation. 10.1111/php.13982 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/php.13982 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_php_13982 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Enhancing PDT efficacy in NMIBC: Efflux inhibitor mediated improvement of PpIX levels and efficacy of the combination of PpIX‐PDT and SO‐cleavable prodrugs Soniya Kumbham Kazi Md Mahabubur Rahman Caroline Bosmajian Ganesh Bist Barbara A. Foster Sukyung Woo Youngjae You Photochemistry and Photobiology Enhancing PDT efficacy in NMIBC: Efflux inhibitor mediated improvement of PpIX levels and efficacy of the combination of PpIX‐PDT and SO‐cleavable prodrugs Soniya Kumbham Kazi Md Mahabubur Rahman Caroline Bosmajian Ganesh Bist Barbara A. Foster Sukyung Woo Youngjae You Photochemistry and Photobiology AbstractProtoporphyrin IX (PpIX)‐based photodynamic therapy (PDT) has shown limited efficacy in nonmuscle‐invasive bladder cancer (NMIBC). To improve PDT efficacy, we developed singlet oxygen‐cleavable prodrugs. These prodrugs, when combined with PpIX‐PDT, induce cancer cell death through both PDT and drug release mechanisms. Inhibition of PpIX efflux was reported to be an effective strategy to improve PpIX‐PDT in certain cancer cells. Our main goal was to investigate whether adding an efflux inhibitor to the combination of PpIX and prodrugs can improve the PpIX levels in bladder cancer cells and the release of active drugs, thus improving the overall efficacy of the treatment. We treated bladder cancer cell lines with lapatinib and evaluated intracellular PpIX fluorescence, finding significantly increased accumulation. Combining lapatinib with prodrugs led to significantly reduced cell viability compared to prodrugs or PpIX‐PDT alone. The effect of lapatinib depended on the expression level of the efflux pump in bladder cancer cells. Interestingly, lapatinib increased paclitaxel (PTX) prodrug uptake by threefold compared to prodrug alone. Adding an efflux inhibitor (e.g., lapatinib) into bladder instillation solutions could be a straightforward and effective strategy for NMIBC treatment, particularly in tumors expressing efflux pumps, with the potential for clinical translation. 10.1111/php.13982 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Enhancing PDT efficacy in NMIBC: Efflux inhibitor mediated improvement of PpIX levels and efficacy of the combination of PpIX‐PDT and SO‐cleavable prodrugs |
| topic | Photochemistry and Photobiology |
| url | https://onlinelibrary.wiley.com/doi/10.1111/php.13982 |