Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy
Abstract Cancer remains a major health challenge, with the effectiveness of chemotherapy often limited by its lack of specificity and systemic toxicity. Nanotechnology, particularly in targeted drug delivery, has emerged as a key innovation to address these limitations. This study introduces lipoic...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56507-4 |
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| author | Liqun Dai Jie Liu Tingyu Yang Xiaorui Yu Yi Lu Lili Pan Siming Zhou Diyun Shu Yuanhao Liu Wuyu Mao Zhiyong Qian |
| author_facet | Liqun Dai Jie Liu Tingyu Yang Xiaorui Yu Yi Lu Lili Pan Siming Zhou Diyun Shu Yuanhao Liu Wuyu Mao Zhiyong Qian |
| author_sort | Liqun Dai |
| collection | DOAJ |
| description | Abstract Cancer remains a major health challenge, with the effectiveness of chemotherapy often limited by its lack of specificity and systemic toxicity. Nanotechnology, particularly in targeted drug delivery, has emerged as a key innovation to address these limitations. This study introduces lipoic acid-boronophenylalanine (LA-BPA) derivatives that incorporate short-chain polyethylene glycol (PEG) as a spacer. These derivatives distinctively self-assemble into vesicles under specific pH conditions, exhibiting a pH-dependent reversible assembly characteristic. Notably, these vesicles target cancer cells by binding to sialic acid via phenylboronic acid groups, subsequently depleting cellular glutathione and elevating reactive oxygen species, thereby inducing apoptosis via mitochondrial dysfunction and mitophagy. The vesicles demonstrate high efficiency in encapsulating doxorubicin, featuring a glutathione-responsive release mechanism, which present a promising option for tumor therapy. Additionally, the derivatives of the B-10 isotope, containing up to 1.6% boron, are engineered for incorporation into L P B-3-based vesicles. This design facilitates their application in boron neutron capture therapy (BNCT) alongside chemotherapy for the treatment of pancreatic cancer. Our findings highlight the potential of LA-BPA derivatives in developing more precise, effective, and less detrimental chemoradiotherapy approaches, marking an advancement in nanomedicine for cancer treatment. |
| format | Article |
| id | doaj-art-051c47677994458292909f2dfb3e1153 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-051c47677994458292909f2dfb3e11532025-02-09T12:44:20ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56507-4Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapyLiqun Dai0Jie Liu1Tingyu Yang2Xiaorui Yu3Yi Lu4Lili Pan5Siming Zhou6Diyun Shu7Yuanhao Liu8Wuyu Mao9Zhiyong Qian10Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNeuboron Medtech Ltd.Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNeuboron Medtech Ltd.Neuboron Medtech Ltd.Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract Cancer remains a major health challenge, with the effectiveness of chemotherapy often limited by its lack of specificity and systemic toxicity. Nanotechnology, particularly in targeted drug delivery, has emerged as a key innovation to address these limitations. This study introduces lipoic acid-boronophenylalanine (LA-BPA) derivatives that incorporate short-chain polyethylene glycol (PEG) as a spacer. These derivatives distinctively self-assemble into vesicles under specific pH conditions, exhibiting a pH-dependent reversible assembly characteristic. Notably, these vesicles target cancer cells by binding to sialic acid via phenylboronic acid groups, subsequently depleting cellular glutathione and elevating reactive oxygen species, thereby inducing apoptosis via mitochondrial dysfunction and mitophagy. The vesicles demonstrate high efficiency in encapsulating doxorubicin, featuring a glutathione-responsive release mechanism, which present a promising option for tumor therapy. Additionally, the derivatives of the B-10 isotope, containing up to 1.6% boron, are engineered for incorporation into L P B-3-based vesicles. This design facilitates their application in boron neutron capture therapy (BNCT) alongside chemotherapy for the treatment of pancreatic cancer. Our findings highlight the potential of LA-BPA derivatives in developing more precise, effective, and less detrimental chemoradiotherapy approaches, marking an advancement in nanomedicine for cancer treatment.https://doi.org/10.1038/s41467-025-56507-4 |
| spellingShingle | Liqun Dai Jie Liu Tingyu Yang Xiaorui Yu Yi Lu Lili Pan Siming Zhou Diyun Shu Yuanhao Liu Wuyu Mao Zhiyong Qian Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy Nature Communications |
| title | Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy |
| title_full | Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy |
| title_fullStr | Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy |
| title_full_unstemmed | Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy |
| title_short | Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy |
| title_sort | lipoic acid boronophenylalanine derived multifunctional vesicles for cancer chemoradiotherapy |
| url | https://doi.org/10.1038/s41467-025-56507-4 |
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