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Advanced Science

Advanced Science

IF: 14.3
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Interleukin 15‐Presenting Nanovesicles with Doxorubicin‐Loaded Ferritin Cores for Cancer Immunochemotherapy

Published:3 December 2024 DOI: 10.1002/advs.202409194 PMID: 39625860
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

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.

Substances (6)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Trypsin 9002-07-7 C35H47N7O10 455 suppliers $17.70-$24930.00
Fluorescein isothiocyanate isomer I 3326-32-7 C21H11NO5S 394 suppliers $37.00-$8352.40
2,3-Dimethylmaleic anhydride 766-39-2 C6H6O3 295 suppliers $10.00-$1590.00
Cy5 146368-15-2 C45H52N4O14S2 101 suppliers Inquiry
FETUIN 9014-81-7 NULL 67 suppliers $37.07-$4380.00
DAPI 47165-04-8 C16H15N5 13 suppliers $504.53-$504.53

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