Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies
Abstract Background Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed h...
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| Format: | Article |
| Language: | English |
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BMC
2021-03-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-021-00786-8 |
| _version_ | 1828136837829361664 |
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| author | Yi-Te Chou Chih-Yu Lin Jyun-Wei Wen Ling-Chun Hung Ying-Feng Chang Chia-Min Yang Li-chen Wu Ja-an Annie Ho |
| author_facet | Yi-Te Chou Chih-Yu Lin Jyun-Wei Wen Ling-Chun Hung Ying-Feng Chang Chia-Min Yang Li-chen Wu Ja-an Annie Ho |
| author_sort | Yi-Te Chou |
| collection | DOAJ |
| description | Abstract Background Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT. Results To achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently. Conclusions Taken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC. |
| first_indexed | 2024-04-11T18:10:10Z |
| format | Article |
| id | doaj.art-d055926de0f145499a2b2fcfe962dc82 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T18:10:10Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-d055926de0f145499a2b2fcfe962dc822022-12-22T04:10:11ZengBMCJournal of Nanobiotechnology1477-31552021-03-0119111510.1186/s12951-021-00786-8Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapiesYi-Te Chou0Chih-Yu Lin1Jyun-Wei Wen2Ling-Chun Hung3Ying-Feng Chang4Chia-Min Yang5Li-chen Wu6Ja-an Annie Ho7BioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan UniversityDepartment of Chemistry, National Tsing Hua UniversityBioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan UniversityBioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan UniversityBioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan UniversityDepartment of Chemistry, National Tsing Hua UniversityDepartment of Applied Chemistry, National Chi Nan UniversityBioAnalytical Chemistry and Nanobiomedicine Laboratory, Department of Biochemical Science and Technology, National Taiwan UniversityAbstract Background Areas of hypoxia are often found in triple-negative breast cancer (TNBC), it is thus more difficult to treat than other types of breast cancer, and may require combination therapies. A new strategy that combined bioreductive therapy with photodynamic therapy (PDT) was developed herein to improve the efficacy of cancer treatment. Our design utilized the characteristics of protoporphyrin IX (PpIX) molecules that reacted and consumed O2 at the tumor site, which led to the production of cytotoxic reactive oxygen species (ROS). The low microenvironmental oxygen levels enabled activation of a bioreductive prodrug, tirapazamine (TPZ), to become a toxic radical. The TPZ radical not only eradicated hypoxic tumor cells, but it also promoted therapeutic efficacy of PDT. Results To achieve the co-delivery of PpIX and TPZ for advanced breast cancer therapy, thin-shell hollow mesoporous Ia3d silica nanoparticles, designated as MMT-2, was employed herein. This nanocarrier designed to target the human breast cancer cell MDA-MB-231 was functionalized with PpIX and DNA aptamer (LXL-1), and loaded with TPZ, resulting in the formation of TPZ@LXL-1-PpIX-MMT-2 nanoVector. A series of studies confirmed that our nanoVectors (TPZ@LXL-1-PpIX-MMT-2) facilitated in vitro and in vivo targeting, and significantly reduced tumor volume in a xenograft mouse model. Histological analysis also revealed that this nanoVector killed tumor cells in hypoxic regions efficiently. Conclusions Taken together, the synergism and efficacy of this new therapeutic design was confirmed. Therefore, we concluded that this new therapeutic strategy, which exploited a complementary combination of PpIX and TPZ, functioned well in both normoxia and hypoxia, and is a promising medical procedure for effective treatment of TNBC.https://doi.org/10.1186/s12951-021-00786-8Triple‐negative breast cancerPhotodynamic therapyTumor hypoxiaBioreductive prodrugHollow mesoporous silica nanoparticleDNA aptamer |
| spellingShingle | Yi-Te Chou Chih-Yu Lin Jyun-Wei Wen Ling-Chun Hung Ying-Feng Chang Chia-Min Yang Li-chen Wu Ja-an Annie Ho Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies Journal of Nanobiotechnology Triple‐negative breast cancer Photodynamic therapy Tumor hypoxia Bioreductive prodrug Hollow mesoporous silica nanoparticle DNA aptamer |
| title | Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies |
| title_full | Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies |
| title_fullStr | Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies |
| title_full_unstemmed | Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies |
| title_short | Targeting triple‐negative breast cancer with an aptamer‐functionalized nanoformulation: a synergistic treatment that combines photodynamic and bioreductive therapies |
| title_sort | targeting triple negative breast cancer with an aptamer functionalized nanoformulation a synergistic treatment that combines photodynamic and bioreductive therapies |
| topic | Triple‐negative breast cancer Photodynamic therapy Tumor hypoxia Bioreductive prodrug Hollow mesoporous silica nanoparticle DNA aptamer |
| url | https://doi.org/10.1186/s12951-021-00786-8 |
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