Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment
Abstract Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed t...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01561-z |
| _version_ | 1817994694321242112 |
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| author | Jun Gu Gang Zhao Jiangkun Yu Pei Xu Jiabin Yan Zhengshuai Jin Sheng Chen Yong Wang Leshuai W. Zhang Yangyun Wang |
| author_facet | Jun Gu Gang Zhao Jiangkun Yu Pei Xu Jiabin Yan Zhengshuai Jin Sheng Chen Yong Wang Leshuai W. Zhang Yangyun Wang |
| author_sort | Jun Gu |
| collection | DOAJ |
| description | Abstract Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects. Graphical Abstract |
| first_indexed | 2024-04-14T01:55:16Z |
| format | Article |
| id | doaj.art-5c0d308366754155b3b7393368d5fc0c |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T01:55:16Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-5c0d308366754155b3b7393368d5fc0c2022-12-22T02:19:07ZengBMCJournal of Nanobiotechnology1477-31552022-08-0120111310.1186/s12951-022-01561-zInjectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironmentJun Gu0Gang Zhao1Jiangkun Yu2Pei Xu3Jiabin Yan4Zhengshuai Jin5Sheng Chen6Yong Wang7Leshuai W. Zhang8Yangyun Wang9The Affiliated Jiangsu Shengze Hospital of Nanjing Medical UniversityState Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityState Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityState Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityThe Affiliated Jiangsu Shengze Hospital of Nanjing Medical UniversityThe Affiliated Jiangsu Shengze Hospital of Nanjing Medical UniversityThe Affiliated Jiangsu Shengze Hospital of Nanjing Medical UniversityState Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityState Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityState Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityAbstract Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01561-zInjectable hydrogelpH-responsiveSilk-chitosan compositeChemoimmunotherapyTumor microenvironment |
| spellingShingle | Jun Gu Gang Zhao Jiangkun Yu Pei Xu Jiabin Yan Zhengshuai Jin Sheng Chen Yong Wang Leshuai W. Zhang Yangyun Wang Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment Journal of Nanobiotechnology Injectable hydrogel pH-responsive Silk-chitosan composite Chemoimmunotherapy Tumor microenvironment |
| title | Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment |
| title_full | Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment |
| title_fullStr | Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment |
| title_full_unstemmed | Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment |
| title_short | Injectable pH-responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment |
| title_sort | injectable ph responsive hydrogel for combinatorial chemoimmunotherapy tailored to the tumor microenvironment |
| topic | Injectable hydrogel pH-responsive Silk-chitosan composite Chemoimmunotherapy Tumor microenvironment |
| url | https://doi.org/10.1186/s12951-022-01561-z |
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