Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer
Due to its noninvasive nature, site-confined irradiation, and high tissue penetrating capabilities, ultrasound (US)-driven sonodynamic treatment (SDT) has been proven to have broad application possibilities in neoplastic and non-neoplastic diseases. However, the inefficient buildup of sonosensitizer...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/14/7981 |
| _version_ | 1797406111107645440 |
|---|---|
| author | Xiaolan Feng Chen Wu Wenhao Yang Jiayi Wu Pan Wang |
| author_facet | Xiaolan Feng Chen Wu Wenhao Yang Jiayi Wu Pan Wang |
| author_sort | Xiaolan Feng |
| collection | DOAJ |
| description | Due to its noninvasive nature, site-confined irradiation, and high tissue penetrating capabilities, ultrasound (US)-driven sonodynamic treatment (SDT) has been proven to have broad application possibilities in neoplastic and non-neoplastic diseases. However, the inefficient buildup of sonosensitizers in the tumor site remarkably impairs SDT efficiency. The present work proposes a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) comprising Pp18 liposomes (Pp18-lipos, Plipo), SRA737 (a CHK1 inhibitor), and doxorubicin (DOX) for the controlled formation of reactive oxygen species (ROS) and release of DOX and SRA737 upon US activation, therefore increasing chemotherapeutic effectiveness and boosting SDT efficacy. Therein, the antitumor activities of DOX have been attributed to its intercalation into the nucleus DNA and induction of cell apoptosis. CHK1 evolved to respond to DNA damage and repair the damage via cell cycle progression. SRA737 is a potent and orally bioavailable clinical drug candidate for inhibiting CHK1, demonstrating adjuvant anticancer effect in vitro and in vivo. It was interesting to find that SRA737 carried into Plipo@DOX could significantly alleviate G2/M cell cycle arrest and aggravate DNA double-strand injuries, resulting in significant cell death. The developed US-switchable nanosystem provides a promising strategy for augmenting sono-chemotherapy against breast cancer controllably and precisely. |
| first_indexed | 2024-03-09T03:20:26Z |
| format | Article |
| id | doaj.art-84c73b6920634413af64ca71b0513532 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:20:26Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-84c73b6920634413af64ca71b05135322023-12-03T15:10:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314798110.3390/ijms23147981Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast CancerXiaolan Feng0Chen Wu1Wenhao Yang2Jiayi Wu3Pan Wang4Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, Xi’an 710119, ChinaKey Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, Xi’an 710119, ChinaKey Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, Xi’an 710119, ChinaKey Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, Xi’an 710119, ChinaKey Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, Ministry of Education, Xi’an 710119, ChinaDue to its noninvasive nature, site-confined irradiation, and high tissue penetrating capabilities, ultrasound (US)-driven sonodynamic treatment (SDT) has been proven to have broad application possibilities in neoplastic and non-neoplastic diseases. However, the inefficient buildup of sonosensitizers in the tumor site remarkably impairs SDT efficiency. The present work proposes a deep-penetrating sonochemistry nanoplatform (Pp18-lipos@SRA737&DOX, PSDL) comprising Pp18 liposomes (Pp18-lipos, Plipo), SRA737 (a CHK1 inhibitor), and doxorubicin (DOX) for the controlled formation of reactive oxygen species (ROS) and release of DOX and SRA737 upon US activation, therefore increasing chemotherapeutic effectiveness and boosting SDT efficacy. Therein, the antitumor activities of DOX have been attributed to its intercalation into the nucleus DNA and induction of cell apoptosis. CHK1 evolved to respond to DNA damage and repair the damage via cell cycle progression. SRA737 is a potent and orally bioavailable clinical drug candidate for inhibiting CHK1, demonstrating adjuvant anticancer effect in vitro and in vivo. It was interesting to find that SRA737 carried into Plipo@DOX could significantly alleviate G2/M cell cycle arrest and aggravate DNA double-strand injuries, resulting in significant cell death. The developed US-switchable nanosystem provides a promising strategy for augmenting sono-chemotherapy against breast cancer controllably and precisely.https://www.mdpi.com/1422-0067/23/14/7981sonodynamic therapyporphyrin liposomesDOXSRA737DNA damage responsebreast cancer |
| spellingShingle | Xiaolan Feng Chen Wu Wenhao Yang Jiayi Wu Pan Wang Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer International Journal of Molecular Sciences sonodynamic therapy porphyrin liposomes DOX SRA737 DNA damage response breast cancer |
| title | Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer |
| title_full | Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer |
| title_fullStr | Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer |
| title_full_unstemmed | Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer |
| title_short | Mechanism-Based Sonodynamic–Chemo Combinations against Triple-Negative Breast Cancer |
| title_sort | mechanism based sonodynamic chemo combinations against triple negative breast cancer |
| topic | sonodynamic therapy porphyrin liposomes DOX SRA737 DNA damage response breast cancer |
| url | https://www.mdpi.com/1422-0067/23/14/7981 |
| work_keys_str_mv | AT xiaolanfeng mechanismbasedsonodynamicchemocombinationsagainsttriplenegativebreastcancer AT chenwu mechanismbasedsonodynamicchemocombinationsagainsttriplenegativebreastcancer AT wenhaoyang mechanismbasedsonodynamicchemocombinationsagainsttriplenegativebreastcancer AT jiayiwu mechanismbasedsonodynamicchemocombinationsagainsttriplenegativebreastcancer AT panwang mechanismbasedsonodynamicchemocombinationsagainsttriplenegativebreastcancer |