aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound
Abstract Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging because of its depth, which often leads to misdiagnosis during ultrasound examinations. The unique PDAC tumor microenvironment (TME) is characterized by significant fibrous tissue growth, and high interstitial pressur...
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BMC
2025-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03105-7 |
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| author | Yi Tang Qingling Shen Peng Lin Zhixin Chen Denghui Fan Minling Zhuo Yajiao Gan Yixi Su Qingfu Qian Liwu Lin Ensheng Xue Zhikui Chen |
| author_facet | Yi Tang Qingling Shen Peng Lin Zhixin Chen Denghui Fan Minling Zhuo Yajiao Gan Yixi Su Qingfu Qian Liwu Lin Ensheng Xue Zhikui Chen |
| author_sort | Yi Tang |
| collection | DOAJ |
| description | Abstract Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging because of its depth, which often leads to misdiagnosis during ultrasound examinations. The unique PDAC tumor microenvironment (TME) is characterized by significant fibrous tissue growth, and high interstitial pressure hinders drug penetration into tumors. Additionally, hypoxia and immune suppression within the tumor contribute to poor responses to radiotherapy and chemotherapy, ultimately leading to an unfavorable prognosis. In this study, aPD-L1-modified docetaxel and perfluoropentane-loaded liquid‒vapor phase-transformation lipid nanoparticles (aPDL1-DTX/PFP@Lipid) were synthesized and had an average diameter of 61.63 nm with 84.3% antibody modification. We demonstrated that the nanoparticles (NPs) exhibited excellent PDAC-targeting capabilities both in vitro and in vivo. Upon exposure to low-intensity pulsed ultrasound (LIPUS) stimulation, the NPs underwent a phase transformation to form microbubbles with substantial molecular ultrasound diagnostic effects, and combined treatment resulted in a tumor growth inhibition rate of 88.91%. This treatment strategy also led to the infiltration of CD8+ T cells, the downregulation of Treg cells, the promotion of M1 macrophage polarization, the inhibition of fibrosis to reduce tumor stromal pressure, and the facilitation of perfluoropentane (PFP) gasification to release O2 and improve tumor hypoxia. In conclusion, aPD-L1-modified liquid‒vapor phase-transformation nanoparticles loaded with docetaxel (DTX) and PFP were successfully combined with ultrasound for the molecular diagnosis and targeted treatment of PDAC. aPDL1-DTX/PFP@Lipid could reshape the PDAC TME, offering a new approach for ultrasound-mediated diagnosis and treatment with promising clinical applications. Graphical Abstract |
| format | Article |
| id | doaj-art-2303c4cb02054d5889321709125eace6 |
| institution | Kabale University |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-2303c4cb02054d5889321709125eace62025-02-02T12:41:18ZengBMCJournal of Nanobiotechnology1477-31552025-01-0123112310.1186/s12951-025-03105-7aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasoundYi Tang0Qingling Shen1Peng Lin2Zhixin Chen3Denghui Fan4Minling Zhuo5Yajiao Gan6Yixi Su7Qingfu Qian8Liwu Lin9Ensheng Xue10Zhikui Chen11Department of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalFujian College Association Instrumental Analysis Center, Fuzhou UniversityDepartment of General Surgery, Affiliated Zhongshan Hospital of Dalian UniversityDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalDepartment of Ultrasound, Fujian Medical University Union HospitalAbstract Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is challenging because of its depth, which often leads to misdiagnosis during ultrasound examinations. The unique PDAC tumor microenvironment (TME) is characterized by significant fibrous tissue growth, and high interstitial pressure hinders drug penetration into tumors. Additionally, hypoxia and immune suppression within the tumor contribute to poor responses to radiotherapy and chemotherapy, ultimately leading to an unfavorable prognosis. In this study, aPD-L1-modified docetaxel and perfluoropentane-loaded liquid‒vapor phase-transformation lipid nanoparticles (aPDL1-DTX/PFP@Lipid) were synthesized and had an average diameter of 61.63 nm with 84.3% antibody modification. We demonstrated that the nanoparticles (NPs) exhibited excellent PDAC-targeting capabilities both in vitro and in vivo. Upon exposure to low-intensity pulsed ultrasound (LIPUS) stimulation, the NPs underwent a phase transformation to form microbubbles with substantial molecular ultrasound diagnostic effects, and combined treatment resulted in a tumor growth inhibition rate of 88.91%. This treatment strategy also led to the infiltration of CD8+ T cells, the downregulation of Treg cells, the promotion of M1 macrophage polarization, the inhibition of fibrosis to reduce tumor stromal pressure, and the facilitation of perfluoropentane (PFP) gasification to release O2 and improve tumor hypoxia. In conclusion, aPD-L1-modified liquid‒vapor phase-transformation nanoparticles loaded with docetaxel (DTX) and PFP were successfully combined with ultrasound for the molecular diagnosis and targeted treatment of PDAC. aPDL1-DTX/PFP@Lipid could reshape the PDAC TME, offering a new approach for ultrasound-mediated diagnosis and treatment with promising clinical applications. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03105-7Contrast-enhanced ultrasoundMolecular diagnosisTargeted therapyTumor microenvironmentPancreatic cancer |
| spellingShingle | Yi Tang Qingling Shen Peng Lin Zhixin Chen Denghui Fan Minling Zhuo Yajiao Gan Yixi Su Qingfu Qian Liwu Lin Ensheng Xue Zhikui Chen aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound Journal of Nanobiotechnology Contrast-enhanced ultrasound Molecular diagnosis Targeted therapy Tumor microenvironment Pancreatic cancer |
| title | aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound |
| title_full | aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound |
| title_fullStr | aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound |
| title_full_unstemmed | aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound |
| title_short | aPD-L1-facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel-loaded phase-transformation nanoparticles triggered by low-intensity pulsed ultrasound |
| title_sort | apd l1 facilitated theranostic and tumor microenvironment remodeling of pancreatic cancer via docetaxel loaded phase transformation nanoparticles triggered by low intensity pulsed ultrasound |
| topic | Contrast-enhanced ultrasound Molecular diagnosis Targeted therapy Tumor microenvironment Pancreatic cancer |
| url | https://doi.org/10.1186/s12951-025-03105-7 |
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