Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy
Summary: In some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), incl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220303291 |
| _version_ | 1828523095739072512 |
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| author | Dong-Bing Cheng Xue-Hao Zhang Yuanfang Chen Hao Chen Zeng-Ying Qiao Hao Wang |
| author_facet | Dong-Bing Cheng Xue-Hao Zhang Yuanfang Chen Hao Chen Zeng-Ying Qiao Hao Wang |
| author_sort | Dong-Bing Cheng |
| collection | DOAJ |
| description | Summary: In some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen 1O2 is generated by P18, (2) the thioketal bond is cleaved by the 1O2, (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy. Thanks to the high tissue-penetrating depth and spatial precision of US, PTPK presents enhanced tumor inhibition in an orthotopic pancreatic tumor model. Therefore, the US-activated cascade effect offers a novel perspective for precision medicine and disease theranostics. |
| first_indexed | 2024-12-11T20:21:15Z |
| format | Article |
| id | doaj.art-d4129379bb3e4a0fb4b1421e45da4dea |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-11T20:21:15Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-d4129379bb3e4a0fb4b1421e45da4dea2022-12-22T00:52:04ZengElsevieriScience2589-00422020-06-01236101144Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer TherapyDong-Bing Cheng0Xue-Hao Zhang1Yuanfang Chen2Hao Chen3Zeng-Ying Qiao4Hao Wang5CAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, ChinaCAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China; College of Science, Huazhong Agricultural University, Wuhan 430070, ChinaCAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, ChinaCollege of Science, Huazhong Agricultural University, Wuhan 430070, ChinaCAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, China; Corresponding authorCAS Center for Excellence in Nanoscience, Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), Beijing 100190, ChinaSummary: In some malignant tumor, especially for pancreatic tumor, poor solid-tumor penetration of nanotherapeutics impedes their treatment efficacy. Herein, we develop a polymer-peptide conjugate with the deep tissue penetration ability, which undergoes a cascade process under ultrasound (US), including (1) the singlet oxygen 1O2 is generated by P18, (2) the thioketal bond is cleaved by the 1O2, (3) the departure of PEG chains leads to the in situ self-assembly, and (4) the resultant self-assembled PK nanoparticles show considerable cellular internalization. Owing to the synergistic effect of US on increasing the membrane permeability, the endocytosis and lysosome escape of PK nanoparticles are further enhanced effectively, resulting in the improved therapeutic efficacy. Thanks to the high tissue-penetrating depth and spatial precision of US, PTPK presents enhanced tumor inhibition in an orthotopic pancreatic tumor model. Therefore, the US-activated cascade effect offers a novel perspective for precision medicine and disease theranostics.http://www.sciencedirect.com/science/article/pii/S2589004220303291CancerNanomaterialsBiomedical Materials |
| spellingShingle | Dong-Bing Cheng Xue-Hao Zhang Yuanfang Chen Hao Chen Zeng-Ying Qiao Hao Wang Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy iScience Cancer Nanomaterials Biomedical Materials |
| title | Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy |
| title_full | Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy |
| title_fullStr | Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy |
| title_full_unstemmed | Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy |
| title_short | Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy |
| title_sort | ultrasound activated cascade effect for synergistic orthotopic pancreatic cancer therapy |
| topic | Cancer Nanomaterials Biomedical Materials |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220303291 |
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