Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment
Abstract Background Although programmed cell death protein 1 (PD-1)/ programmed cell death-ligand protein 1 (PD-L1) checkpoint blockade immunotherapy demonstrates great promise in cancer treatment, poor infiltration of T cells resulted from tumor immunosuppressive microenvironment (TIME) and insuffi...
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2023-02-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40824-023-00350-5 |
| _version_ | 1827332004575707136 |
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| author | Jun Zheng Ju Huang Liang Zhang Mengna Wang Lihong Xu Xiaoyun Dou Xiaojing Leng Mingxiao Fang Yang Sun Zhigang Wang |
| author_facet | Jun Zheng Ju Huang Liang Zhang Mengna Wang Lihong Xu Xiaoyun Dou Xiaojing Leng Mingxiao Fang Yang Sun Zhigang Wang |
| author_sort | Jun Zheng |
| collection | DOAJ |
| description | Abstract Background Although programmed cell death protein 1 (PD-1)/ programmed cell death-ligand protein 1 (PD-L1) checkpoint blockade immunotherapy demonstrates great promise in cancer treatment, poor infiltration of T cells resulted from tumor immunosuppressive microenvironment (TIME) and insufficient accumulation of anti-PD-L1 (αPD-L1) in tumor sites diminish the immune response. Herein, we reported a drug-loaded microbubble delivery system to overcome these obstacles and enhance PD-L1 blockade immunotherapy. Methods Docetaxel (DTX) and imiquimod (R837)-loaded microbubbles (RD@MBs) were synthesized via a typical rotary evaporation method combined with mechanical oscillation. The targeted release of drugs was achieved by using the directional "bursting" capability of ultrasound-targeted microbubble destruction (UTMD) technology. The antitumor immune response by RD@MBs combining αPD-L1 were evaluated on 4T1 and CT26 tumor models. Results The dying tumor cells induced by DTX release tumor-associated antigens (TAAs), together with R837, promoted the activation, proliferation and recruitment of T cells. Besides, UTMD technology and DTX enhanced the accumulation of αPD-L1 in tumor sites. Moreover, RD@MBs remolded TIME, including the polarization of M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, and reduction of myeloid-derived suppressor cells (MDSCs). The RD@MBs + αPD-L1 synergistic therapy not only effectively inhibited the growth of primary tumors, but also significantly inhibited the mimic distant tumors as well as lung metastases. Conclusion PD-L1 blockade immunotherapy was enhanced by RD@MBs delivery system. |
| first_indexed | 2024-03-07T16:49:35Z |
| format | Article |
| id | doaj.art-d7f0490c6ae5406d9086bab6828c1c87 |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T16:49:35Z |
| publishDate | 2023-02-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Biomaterials Research |
| spelling | doaj.art-d7f0490c6ae5406d9086bab6828c1c872024-03-03T05:43:33ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242023-02-0127112210.1186/s40824-023-00350-5Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironmentJun Zheng0Ju Huang1Liang Zhang2Mengna Wang3Lihong Xu4Xiaoyun Dou5Xiaojing Leng6Mingxiao Fang7Yang Sun8Zhigang Wang9State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityState Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityState Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityDepartment of Pathology, College of Basic Medicine, Chongqing Medical UniversityInstitute of Life Sciences, Chongqing Medical UniversityInstitute of Life Sciences, Chongqing Medical UniversityState Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityState Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityState Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityState Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical UniversityAbstract Background Although programmed cell death protein 1 (PD-1)/ programmed cell death-ligand protein 1 (PD-L1) checkpoint blockade immunotherapy demonstrates great promise in cancer treatment, poor infiltration of T cells resulted from tumor immunosuppressive microenvironment (TIME) and insufficient accumulation of anti-PD-L1 (αPD-L1) in tumor sites diminish the immune response. Herein, we reported a drug-loaded microbubble delivery system to overcome these obstacles and enhance PD-L1 blockade immunotherapy. Methods Docetaxel (DTX) and imiquimod (R837)-loaded microbubbles (RD@MBs) were synthesized via a typical rotary evaporation method combined with mechanical oscillation. The targeted release of drugs was achieved by using the directional "bursting" capability of ultrasound-targeted microbubble destruction (UTMD) technology. The antitumor immune response by RD@MBs combining αPD-L1 were evaluated on 4T1 and CT26 tumor models. Results The dying tumor cells induced by DTX release tumor-associated antigens (TAAs), together with R837, promoted the activation, proliferation and recruitment of T cells. Besides, UTMD technology and DTX enhanced the accumulation of αPD-L1 in tumor sites. Moreover, RD@MBs remolded TIME, including the polarization of M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, and reduction of myeloid-derived suppressor cells (MDSCs). The RD@MBs + αPD-L1 synergistic therapy not only effectively inhibited the growth of primary tumors, but also significantly inhibited the mimic distant tumors as well as lung metastases. Conclusion PD-L1 blockade immunotherapy was enhanced by RD@MBs delivery system.https://doi.org/10.1186/s40824-023-00350-5Ultrasound-targeted microbubble destruction (UTMD)Immune checkpoint blockade (ICB)Docetaxel (DTX)PD-L1Tumor immunosuppressive microenvironment |
| spellingShingle | Jun Zheng Ju Huang Liang Zhang Mengna Wang Lihong Xu Xiaoyun Dou Xiaojing Leng Mingxiao Fang Yang Sun Zhigang Wang Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment Biomaterials Research Ultrasound-targeted microbubble destruction (UTMD) Immune checkpoint blockade (ICB) Docetaxel (DTX) PD-L1 Tumor immunosuppressive microenvironment |
| title | Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment |
| title_full | Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment |
| title_fullStr | Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment |
| title_full_unstemmed | Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment |
| title_short | Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment |
| title_sort | drug loaded microbubble delivery system to enhance pd l1 blockade immunotherapy with remodeling immune microenvironment |
| topic | Ultrasound-targeted microbubble destruction (UTMD) Immune checkpoint blockade (ICB) Docetaxel (DTX) PD-L1 Tumor immunosuppressive microenvironment |
| url | https://doi.org/10.1186/s40824-023-00350-5 |
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