Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer
Liver cancer is an aggressive malignancy associated with high levels of mortality and morbidity. Doxorubicin (Dox) is often used to slow down liver cancer progression; however its efficacy is limited, and its severe side effects prevent its routine use at therapeutic concentrations. We present a bio...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/155233 |
| _version_ | 1811691518397775872 |
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| author | Lim, Zhi Wei Varma, Vijaykumar B. Ramanujan, Raju V. Miserez, Ali |
| author2 | School of Materials Science and Engineering |
| author_facet | School of Materials Science and Engineering Lim, Zhi Wei Varma, Vijaykumar B. Ramanujan, Raju V. Miserez, Ali |
| author_sort | Lim, Zhi Wei |
| collection | NTU |
| description | Liver cancer is an aggressive malignancy associated with high levels of mortality and morbidity. Doxorubicin (Dox) is often used to slow down liver cancer progression; however its efficacy is limited, and its severe side effects prevent its routine use at therapeutic concentrations. We present a biomimetic peptide that coacervates into micro-droplets, within which both Dox and magnetic nanoparticles (MNPs) can be sequestered. These Dox-loaded Magnetic Coacervates (DMCs) can be used for thermo-chemotherapy, with the controlled release of Dox triggered by an external Alternating Magnetic Field (AMF). The DMCs are internalized by the cells via an energy-independent mechanism which is not based on endocytosis. Application of AMF generates a temperature of 45 °C within the DMCs, triggering their disassembly and the simultaneous release of Dox, thereby resulting in dual hyperthermia and chemotherapy for more efficient cancer therapy. In vitro studies conducted under AMF reveal that DMCs are cytocompatible and effective in inducing HepG2 liver cancer cell death. Thermo-chemotherapy treatment against HepG2 cells is also shown to be more effective compared to either hyperthermia or chemotherapy treatments alone. Thus, our novel peptide DMCs can open avenues in theranostic strategies against liver cancer through programmable, wireless, and remote control of Dox release. STATEMENT OF SIGNIFICANCE: Simultaneous administration of chemical and thermal therapy (thermo-chemotherapy) is more effective in inducing liver cancer cell death and improving survival rate. Thus, there is a keen interest in developing suitable carriers for thermo-chemotherapy. Coacervate micro-droplets display significant advantages, including high loading capacity, fast self-assembly in aqueous environments, and liquid-like behavior. However, they have not yet been explored as carriers for thermo-chemotherapy. Here, we demonstrate that peptide coacervate micro-droplets can co-encapsulate Dox and magnetic nanoparticles and cross the cell membrane. Applying an alternating magnetic field to cells containing drug-loaded coacervates triggers the release of Dox as well as the localized heating by magnetic hyperthermia, resulting in efficient liver cancer cell death by dual thermo-chemotherapy. |
| first_indexed | 2024-10-01T06:21:10Z |
| format | Journal Article |
| id | ntu-10356/155233 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:21:10Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1552332022-03-01T06:45:40Z Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer Lim, Zhi Wei Varma, Vijaykumar B. Ramanujan, Raju V. Miserez, Ali School of Materials Science and Engineering School of Biological Sciences Science::Biological sciences Coacervates Doxorubicin Liver cancer is an aggressive malignancy associated with high levels of mortality and morbidity. Doxorubicin (Dox) is often used to slow down liver cancer progression; however its efficacy is limited, and its severe side effects prevent its routine use at therapeutic concentrations. We present a biomimetic peptide that coacervates into micro-droplets, within which both Dox and magnetic nanoparticles (MNPs) can be sequestered. These Dox-loaded Magnetic Coacervates (DMCs) can be used for thermo-chemotherapy, with the controlled release of Dox triggered by an external Alternating Magnetic Field (AMF). The DMCs are internalized by the cells via an energy-independent mechanism which is not based on endocytosis. Application of AMF generates a temperature of 45 °C within the DMCs, triggering their disassembly and the simultaneous release of Dox, thereby resulting in dual hyperthermia and chemotherapy for more efficient cancer therapy. In vitro studies conducted under AMF reveal that DMCs are cytocompatible and effective in inducing HepG2 liver cancer cell death. Thermo-chemotherapy treatment against HepG2 cells is also shown to be more effective compared to either hyperthermia or chemotherapy treatments alone. Thus, our novel peptide DMCs can open avenues in theranostic strategies against liver cancer through programmable, wireless, and remote control of Dox release. STATEMENT OF SIGNIFICANCE: Simultaneous administration of chemical and thermal therapy (thermo-chemotherapy) is more effective in inducing liver cancer cell death and improving survival rate. Thus, there is a keen interest in developing suitable carriers for thermo-chemotherapy. Coacervate micro-droplets display significant advantages, including high loading capacity, fast self-assembly in aqueous environments, and liquid-like behavior. However, they have not yet been explored as carriers for thermo-chemotherapy. Here, we demonstrate that peptide coacervate micro-droplets can co-encapsulate Dox and magnetic nanoparticles and cross the cell membrane. Applying an alternating magnetic field to cells containing drug-loaded coacervates triggers the release of Dox as well as the localized heating by magnetic hyperthermia, resulting in efficient liver cancer cell death by dual thermo-chemotherapy. Ministry of Education (MOE) Nanyang Technological University This research was funded by the Singapore Ministry of Education (MOE) through an Academic Research Fund (AcRF) Tier 2 Grant (# MOE2015-T2-1–062). We also acknowledge financial support from the Strategic Initiative on Biomimetic and Sustainable Materials (IBSM) at NTU. We thank Prof. Yansong Miao and Zhiming Ma (NTU) for access and support with FRAP experiments. 2022-03-01T06:45:40Z 2022-03-01T06:45:40Z 2020 Journal Article Lim, Z. W., Varma, V. B., Ramanujan, R. V. & Miserez, A. (2020). Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer. Acta Biomaterialia, 110, 221-230. https://dx.doi.org/10.1016/j.actbio.2020.04.024 1742-7061 https://hdl.handle.net/10356/155233 10.1016/j.actbio.2020.04.024 32422317 2-s2.0-85084989056 110 221 230 en MOE2015-T2-1–062 Acta Biomaterialia © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved |
| spellingShingle | Science::Biological sciences Coacervates Doxorubicin Lim, Zhi Wei Varma, Vijaykumar B. Ramanujan, Raju V. Miserez, Ali Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| title | Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| title_full | Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| title_fullStr | Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| title_full_unstemmed | Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| title_short | Magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| title_sort | magnetically responsive peptide coacervates for dual hyperthermia and chemotherapy treatments of liver cancer |
| topic | Science::Biological sciences Coacervates Doxorubicin |
| url | https://hdl.handle.net/10356/155233 |
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