Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems
Exosomes are extracellular nanovesicles secreted by cells that efficiently deliver therapeutic cargo for cancer treatment. However, because exosomes are present in low quantities and have limited target specificity, internal and external stress stimulation has been studied to increase exosome effici...
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2024-11-01
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| author | MinSeok Kim YounJoong Kim ChiYeon Hwang MinHyeok Song SuKang Kim Kyung-Sik Yoon InSug Kang HyungHwan Baik Yong-Jin Yoon |
| author_facet | MinSeok Kim YounJoong Kim ChiYeon Hwang MinHyeok Song SuKang Kim Kyung-Sik Yoon InSug Kang HyungHwan Baik Yong-Jin Yoon |
| author_sort | MinSeok Kim |
| collection | DOAJ |
| description | Exosomes are extracellular nanovesicles secreted by cells that efficiently deliver therapeutic cargo for cancer treatment. However, because exosomes are present in low quantities and have limited target specificity, internal and external stress stimulation has been studied to increase exosome efficiency. Inspired by these studies, the uptake efficiency of cobalt chloride-induced hypoxic cancer cell-secreted exosomes was evaluated. Western blotting and RT-PCR data revealed increased exosome secretion and different protein compositions exhibited by hypoxic exosomes (H-Exos) compared to natural normoxic exosomes (N-Exos). Furthermore, these H-Exos were continuously stimulated using low-intensity ultrasound (LICUS) at an intensity of 360 mW/cm<sup>2</sup> and a frequency of 3 MHz in vitro and 1 MHz in vivo. Hyperthermic and mechanical stress caused by ultrasound successfully improved exosome uptake via clathrin-mediated pathways, and confocal laser microscopy showed strong internal localization near the target cell nuclei. Finally, LICUS-equipped H-Exos were loaded with hydrophobic curcumin (H-Exo-Cur) and used to treat parent HepG2 liver cancer cells. The UV–Vis spectrophotometer displayed enhanced stability, solubility, and concentration of the encapsulated drug molecules. In MTT and FACS studies, approximately 40 times higher cell death was induced, and in animal studies, approximately 10 times higher tumor sizes were suppressed by LICUS-assisted H-Exo-Cur compared to the control. In this study, the delivery platform constructed demonstrated enormous potential for liver cancer therapy. |
| format | Article |
| id | doaj-art-b179543f5c6d438ca647adc437541fa2 |
| institution | DOAJ |
| issn | 2306-5354 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj-art-b179543f5c6d438ca647adc437541fa22025-08-20T02:50:56ZengMDPI AGBioengineering2306-53542024-11-011112118410.3390/bioengineering11121184Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery SystemsMinSeok Kim0YounJoong Kim1ChiYeon Hwang2MinHyeok Song3SuKang Kim4Kyung-Sik Yoon5InSug Kang6HyungHwan Baik7Yong-Jin Yoon8Department of Medicine, Graduate School, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Structural Biology and Biophysics, University of Connecticut, Storrs, CT 06269, USADepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Biomedical Laboratory Science, Catholic Kwandong University, Gangneung 25601, Republic of KoreaDepartment of Medicine, Graduate School, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Medicine, Graduate School, Kyung Hee University, Seoul 02453, Republic of KoreaDepartment of Mechanical Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of KoreaExosomes are extracellular nanovesicles secreted by cells that efficiently deliver therapeutic cargo for cancer treatment. However, because exosomes are present in low quantities and have limited target specificity, internal and external stress stimulation has been studied to increase exosome efficiency. Inspired by these studies, the uptake efficiency of cobalt chloride-induced hypoxic cancer cell-secreted exosomes was evaluated. Western blotting and RT-PCR data revealed increased exosome secretion and different protein compositions exhibited by hypoxic exosomes (H-Exos) compared to natural normoxic exosomes (N-Exos). Furthermore, these H-Exos were continuously stimulated using low-intensity ultrasound (LICUS) at an intensity of 360 mW/cm<sup>2</sup> and a frequency of 3 MHz in vitro and 1 MHz in vivo. Hyperthermic and mechanical stress caused by ultrasound successfully improved exosome uptake via clathrin-mediated pathways, and confocal laser microscopy showed strong internal localization near the target cell nuclei. Finally, LICUS-equipped H-Exos were loaded with hydrophobic curcumin (H-Exo-Cur) and used to treat parent HepG2 liver cancer cells. The UV–Vis spectrophotometer displayed enhanced stability, solubility, and concentration of the encapsulated drug molecules. In MTT and FACS studies, approximately 40 times higher cell death was induced, and in animal studies, approximately 10 times higher tumor sizes were suppressed by LICUS-assisted H-Exo-Cur compared to the control. In this study, the delivery platform constructed demonstrated enormous potential for liver cancer therapy.https://www.mdpi.com/2306-5354/11/12/1184exosomedrug delivery systemlow-intensity ultrasoundhypoxiacurcumin |
| spellingShingle | MinSeok Kim YounJoong Kim ChiYeon Hwang MinHyeok Song SuKang Kim Kyung-Sik Yoon InSug Kang HyungHwan Baik Yong-Jin Yoon Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems Bioengineering exosome drug delivery system low-intensity ultrasound hypoxia curcumin |
| title | Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems |
| title_full | Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems |
| title_fullStr | Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems |
| title_full_unstemmed | Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems |
| title_short | Low-Intensity Continuous Ultrasound Enhances the Therapeutic Efficacy of Curcumin-Encapsulated Exosomes Derived from Hypoxic Liver Cancer Cells via Homotropic Drug Delivery Systems |
| title_sort | low intensity continuous ultrasound enhances the therapeutic efficacy of curcumin encapsulated exosomes derived from hypoxic liver cancer cells via homotropic drug delivery systems |
| topic | exosome drug delivery system low-intensity ultrasound hypoxia curcumin |
| url | https://www.mdpi.com/2306-5354/11/12/1184 |
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