Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy
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.
Authors
- Yihui Zhai (ORCID: https://orcid.org/0000-0001-7593-5538)
- Rong Rong (ORCID: https://orcid.org/0000-0003-2423-4082)
- Helen He Zhu (ORCID: https://orcid.org/0000-0003-0290-5527)
- Yang Yu (ORCID: https://orcid.org/0000-0003-4432-3955)
- Pengcheng Zhang (ORCID: https://orcid.org/0000-0002-4546-0022)
- Wen Zhang (ORCID: https://orcid.org/0000-0003-3150-2751)
- Yaping Li (ORCID: https://orcid.org/0000-0002-0574-6966)
- Ying Cai (ORCID: https://orcid.org/0000-0002-1782-719X)
- Jinming Wang (ORCID: https://orcid.org/0000-0002-2452-9158)
- Chao Zheng (ORCID: https://orcid.org/0000-0002-7051-0925)
- Ying Kong (ORCID: https://orcid.org/0000-0003-4349-6686)
- Yanke Wang
- Tianqun Lang (ORCID: https://orcid.org/0009-0001-0136-3132)
Institutions
- Shanghai Jiao Tong University (CN)
- Chinese Academy of Sciences (CN)
- ShanghaiTech University (CN)
- Xinjiang Institute of Materia Medica (CN)
- Yantai Institute of Coastal Zone Research (CN)
- Shanghai Institute of Materia Medica (CN)
- State Key Laboratory of Oncogene and Related Genes (CN)
- Shanghai Clinical Research Center (CN)
- Shanghai Institute of Pharmaceutical Industry (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Advanced Science
- Published
- 2024-12-03
- DOI
- https://doi.org/10.1002/advs.202409194
- Citations
- 7
- Primary Topic
- Immune Cell Function and Interaction
- Type
- article
- Field-Weighted Citation Impact
- 1.68
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- National Key Research and Development Program of China
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences