Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy
Abstract Interleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non‐specific sti...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202409194 |
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| author | Yihui Zhai Wen Zhang Jinming Wang Ying Kong Rong Rong Tianqun Lang Chao Zheng Yanke Wang Yang Yu Helen He Zhu Ying Cai Pengcheng Zhang Yaping Li |
| author_facet | Yihui Zhai Wen Zhang Jinming Wang Ying Kong Rong Rong Tianqun Lang Chao Zheng Yanke Wang Yang Yu Helen He Zhu Ying Cai Pengcheng Zhang Yaping Li |
| author_sort | Yihui Zhai |
| collection | DOAJ |
| description | Abstract Interleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non‐specific stimulation of cancer cells. Herein, a nanovesicle termed DoxFILN, comprising a membrane presenting IL15/IL15 receptor α complexes (IL15c) and a core of doxorubicin‐loaded ferritin (Dox‐Fn) are reported. The DoxFILN significantly enhances the densities and activities of intratumoral CTLs and NK cells. Mechanistically, DoxFILN undergoes deshelling in the acidic tumor microenvironment, releasing Dox‐Fn and membrane‐bound IL15c. Dox‐Fn selectively target transferrin receptors on cancerous cells, facilitating intracellular Dox release and inducing immunogenic cell death. Concurrently, membrane‐bound IL15c recognizes and activates IL15 receptor β/γc heterodimers, leading to a remarkable increase in the proliferation and activation of CTLs (16‐fold and 28‐fold) and NK cells (37‐fold and 50‐fold). The IL15‐displaying nanovesicle introduced here holds promise as a potential platform for immunochemotherapy in the treatment of cancer. |
| format | Article |
| id | doaj-art-aa001b0685624c029ba54e0f04cb1970 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-aa001b0685624c029ba54e0f04cb19702025-01-29T09:50:18ZengWileyAdvanced Science2198-38442025-01-01124n/an/a10.1002/advs.202409194Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer ImmunochemotherapyYihui Zhai0Wen Zhang1Jinming Wang2Ying Kong3Rong Rong4Tianqun Lang5Chao Zheng6Yanke Wang7Yang Yu8Helen He Zhu9Ying Cai10Pengcheng Zhang11Yaping Li12State Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Road Shanghai 201203 ChinaState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaState Key Laboratory of Oncogenes and Related Genes Renji‐Med‐X Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine and School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200127 ChinaYantai Institute of Materia Medica Shandong 264000 ChinaYantai Institute of Materia Medica Shandong 264000 ChinaState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Road Shanghai 201203 ChinaState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaNational Facility for Protein Science in Shanghai Zhangjiang Lab Shanghai 201210 ChinaNational Facility for Protein Science in Shanghai Zhangjiang Lab Shanghai 201210 ChinaState Key Laboratory of Oncogenes and Related Genes Renji‐Med‐X Stem Cell Research Center Department of Urology Ren Ji Hospital School of Medicine and School of Biomedical Engineering Shanghai Jiao Tong University Shanghai 200127 ChinaState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Road Shanghai 201203 ChinaSchool of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech University Shanghai 201210 ChinaState Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Road Shanghai 201203 ChinaAbstract Interleukin 15 (IL15) is crucial for fostering the survival and proliferation of nature killer (NK) cells and cytotoxic T lymphocytes (CTLs), playing a pivotal role in tumor control. However, IL15 supplementary therapy encounters challenges such as systemic inflammation and non‐specific stimulation of cancer cells. Herein, a nanovesicle termed DoxFILN, comprising a membrane presenting IL15/IL15 receptor α complexes (IL15c) and a core of doxorubicin‐loaded ferritin (Dox‐Fn) are reported. The DoxFILN significantly enhances the densities and activities of intratumoral CTLs and NK cells. Mechanistically, DoxFILN undergoes deshelling in the acidic tumor microenvironment, releasing Dox‐Fn and membrane‐bound IL15c. Dox‐Fn selectively target transferrin receptors on cancerous cells, facilitating intracellular Dox release and inducing immunogenic cell death. Concurrently, membrane‐bound IL15c recognizes and activates IL15 receptor β/γc heterodimers, leading to a remarkable increase in the proliferation and activation of CTLs (16‐fold and 28‐fold) and NK cells (37‐fold and 50‐fold). The IL15‐displaying nanovesicle introduced here holds promise as a potential platform for immunochemotherapy in the treatment of cancer.https://doi.org/10.1002/advs.202409194CTLsIL15, immunotherapynanovesiclesNK cells |
| spellingShingle | Yihui Zhai Wen Zhang Jinming Wang Ying Kong Rong Rong Tianqun Lang Chao Zheng Yanke Wang Yang Yu Helen He Zhu Ying Cai Pengcheng Zhang Yaping Li Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy Advanced Science CTLs IL15, immunotherapy nanovesicles NK cells |
| title | Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy |
| title_full | Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy |
| title_fullStr | Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy |
| title_full_unstemmed | Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy |
| title_short | Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy |
| title_sort | interleukin 15 presenting nanovesicles with doxorubicin loaded ferritin cores for cancer immunochemotherapy |
| topic | CTLs IL15, immunotherapy nanovesicles NK cells |
| url | https://doi.org/10.1002/advs.202409194 |
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