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| Natura: | Artículo Open Access |
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Wiley
2025
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| Accesso online: | https://onlinelibrary.wiley.com/doi/10.1111/php.70057 |
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| _version_ | 1867009516446416896 |
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| author | Jordyn Olsen Sharayu Chandratre Lolwah Alsalamah Daniel Merenich Kenneth A. Myers Bin Chen |
| author_facet | Jordyn Olsen Sharayu Chandratre Lolwah Alsalamah Daniel Merenich Kenneth A. Myers Bin Chen Jordyn Olsen Sharayu Chandratre Lolwah Alsalamah Daniel Merenich Kenneth A. Myers Bin Chen |
| collection | Wiley Open Access |
| contents | Combination of iron chelator deferoxamine and ABCG2 transporter inhibitor lapatinib for therapeutic enhancement of 5‐aminolevulinic acid Jordyn Olsen Sharayu Chandratre Lolwah Alsalamah Daniel Merenich Kenneth A. Myers Bin Chen Photochemistry and Photobiology Abstract The use of 5‐aminolevulinic acid (ALA)‐induced protoporphyrin IX (PpIX) for tumor fluorescence imaging and photodynamic therapy (PDT) may be limited by intrinsic PpIX‐reducing mechanisms including PpIX bioconversion and efflux transport. The effectiveness of targeting these PpIX‐reducing mechanisms was evaluated in glioblastoma cell lines. Although either inhibiting PpIX bioconversion by an iron chelator deferoxamine (DFO) or suppressing PpIX efflux by an ABCG2 transporter inhibitor lapatinib (Lap) significantly increased ALA‐PpIX and PDT effect in the A172 cell line with weak ABCG2 activity, DFO in combination with Lap led to significantly greater enhancement effects. However, DFO did not significantly enhance ALA in H4, U‐87, and U‐118 cell lines with robust ABCG2 activities, whereas Lap showed effective enhancement effects. The combination of DFO and Lap enhanced ALA‐induced PpIX and PDT in these three cell lines. Not just increasing ALA‐PpIX levels, Lap enhanced PpIX localization in the mitochondria and promoted mitochondria‐mediated apoptosis after PDT in the H4 cell line with strong ABCG2 activities. Our results demonstrate that blocking ABCG2‐mediated PpIX efflux is critical for the enhancement of ALA and, in tumor cells with ABCG2 activities, inhibiting PpIX bioconversion by DFO needs to be combined with PpIX efflux suppression for effective enhancement of ALA. 10.1111/php.70057 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/php.70057 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_php_70057 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Combination of iron chelator deferoxamine and ABCG2 transporter inhibitor lapatinib for therapeutic enhancement of 5‐aminolevulinic acid Jordyn Olsen Sharayu Chandratre Lolwah Alsalamah Daniel Merenich Kenneth A. Myers Bin Chen Photochemistry and Photobiology Combination of iron chelator deferoxamine and ABCG2 transporter inhibitor lapatinib for therapeutic enhancement of 5‐aminolevulinic acid Jordyn Olsen Sharayu Chandratre Lolwah Alsalamah Daniel Merenich Kenneth A. Myers Bin Chen Photochemistry and Photobiology Abstract The use of 5‐aminolevulinic acid (ALA)‐induced protoporphyrin IX (PpIX) for tumor fluorescence imaging and photodynamic therapy (PDT) may be limited by intrinsic PpIX‐reducing mechanisms including PpIX bioconversion and efflux transport. The effectiveness of targeting these PpIX‐reducing mechanisms was evaluated in glioblastoma cell lines. Although either inhibiting PpIX bioconversion by an iron chelator deferoxamine (DFO) or suppressing PpIX efflux by an ABCG2 transporter inhibitor lapatinib (Lap) significantly increased ALA‐PpIX and PDT effect in the A172 cell line with weak ABCG2 activity, DFO in combination with Lap led to significantly greater enhancement effects. However, DFO did not significantly enhance ALA in H4, U‐87, and U‐118 cell lines with robust ABCG2 activities, whereas Lap showed effective enhancement effects. The combination of DFO and Lap enhanced ALA‐induced PpIX and PDT in these three cell lines. Not just increasing ALA‐PpIX levels, Lap enhanced PpIX localization in the mitochondria and promoted mitochondria‐mediated apoptosis after PDT in the H4 cell line with strong ABCG2 activities. Our results demonstrate that blocking ABCG2‐mediated PpIX efflux is critical for the enhancement of ALA and, in tumor cells with ABCG2 activities, inhibiting PpIX bioconversion by DFO needs to be combined with PpIX efflux suppression for effective enhancement of ALA. 10.1111/php.70057 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Combination of iron chelator deferoxamine and ABCG2 transporter inhibitor lapatinib for therapeutic enhancement of 5‐aminolevulinic acid |
| topic | Photochemistry and Photobiology |
| url | https://onlinelibrary.wiley.com/doi/10.1111/php.70057 |