Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice
Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its antican...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3101 |
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| author | Kenan Aloss Syeda Mahak Zahra Bokhari Pedro Henrique Leroy Viana Nino Giunashvili Csaba András Schvarcz Gábor Szénási Dániel Bócsi Zoltán Koós Gert Storm Zsuzsanna Miklós Zoltán Benyó Péter Hamar |
| author_facet | Kenan Aloss Syeda Mahak Zahra Bokhari Pedro Henrique Leroy Viana Nino Giunashvili Csaba András Schvarcz Gábor Szénási Dániel Bócsi Zoltán Koós Gert Storm Zsuzsanna Miklós Zoltán Benyó Péter Hamar |
| author_sort | Kenan Aloss |
| collection | DOAJ |
| description | Modulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). The 4T1 cells were orthotopically injected into Balb/C mice, and mEHT was performed on days 9, 12, and 15 after the implantation. DOX, LTLD, or PEGylated liposomal DOX (PLD) were administered for comparison. The tumor size and DOX accumulation in the tumor were measured. The cleaved caspase-3 (cC3) and cell proliferation were evaluated by cC3 or Ki67 immunohistochemistry and Western blot. The LTLD+mEHT combination was more effective at inhibiting tumor growth than the free DOX and PLD, demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the tumor one hour after treatment. Tumor cell damage was associated with cC3 in the damaged area, and with a reduction in Ki67 in the living area. These changes were significantly the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue. |
| first_indexed | 2024-04-24T18:12:52Z |
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| id | doaj.art-d628f93e5d2f4bd0bac481bc6d86149a |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:12:52Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d628f93e5d2f4bd0bac481bc6d86149a2024-03-27T13:45:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256310110.3390/ijms25063101Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing MiceKenan Aloss0Syeda Mahak Zahra Bokhari1Pedro Henrique Leroy Viana2Nino Giunashvili3Csaba András Schvarcz4Gábor Szénási5Dániel Bócsi6Zoltán Koós7Gert Storm8Zsuzsanna Miklós9Zoltán Benyó10Péter Hamar11Institute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3508 Utrecht, The NetherlandsInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryInstitute of Translational Medicine, Semmelweis University, 1094 Budapest, HungaryModulated electro-hyperthermia (mEHT) is an adjuvant cancer therapy that enables tumor-selective heating (+2.5 °C). In this study, we investigated whether mEHT accelerates the tumor-specific delivery of doxorubicin (DOX) from lyso-thermosensitive liposomal doxorubicin (LTLD) and improves its anticancer efficacy in mice bearing a triple-negative breast cancer cell line (4T1). The 4T1 cells were orthotopically injected into Balb/C mice, and mEHT was performed on days 9, 12, and 15 after the implantation. DOX, LTLD, or PEGylated liposomal DOX (PLD) were administered for comparison. The tumor size and DOX accumulation in the tumor were measured. The cleaved caspase-3 (cC3) and cell proliferation were evaluated by cC3 or Ki67 immunohistochemistry and Western blot. The LTLD+mEHT combination was more effective at inhibiting tumor growth than the free DOX and PLD, demonstrated by reductions in both the tumor volume and tumor weight. LTLD+mEHT resulted in the highest DOX accumulation in the tumor one hour after treatment. Tumor cell damage was associated with cC3 in the damaged area, and with a reduction in Ki67 in the living area. These changes were significantly the strongest in the LTLD+mEHT-treated tumors. The body weight loss was similar in all mice treated with any DOX formulation, suggesting no difference in toxicity. In conclusion, LTLD combined with mEHT represents a novel approach for DOX delivery into cancer tissue.https://www.mdpi.com/1422-0067/25/6/3101modulated electro-hyperthermiadoxorubicinlyso-thermosensitive liposomePEGylated liposome |
| spellingShingle | Kenan Aloss Syeda Mahak Zahra Bokhari Pedro Henrique Leroy Viana Nino Giunashvili Csaba András Schvarcz Gábor Szénási Dániel Bócsi Zoltán Koós Gert Storm Zsuzsanna Miklós Zoltán Benyó Péter Hamar Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice International Journal of Molecular Sciences modulated electro-hyperthermia doxorubicin lyso-thermosensitive liposome PEGylated liposome |
| title | Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice |
| title_full | Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice |
| title_fullStr | Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice |
| title_full_unstemmed | Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice |
| title_short | Modulated Electro-Hyperthermia Accelerates Tumor Delivery and Improves Anticancer Activity of Doxorubicin Encapsulated in Lyso-Thermosensitive Liposomes in 4T1-Tumor-Bearing Mice |
| title_sort | modulated electro hyperthermia accelerates tumor delivery and improves anticancer activity of doxorubicin encapsulated in lyso thermosensitive liposomes in 4t1 tumor bearing mice |
| topic | modulated electro-hyperthermia doxorubicin lyso-thermosensitive liposome PEGylated liposome |
| url | https://www.mdpi.com/1422-0067/25/6/3101 |
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