journal article·2025-01Open access

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

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

Advanced Science· Volume 12· Issue 4

Abstract

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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Immune Cell Function and Interaction · Immunotherapy and Immune Responses · HIV Research and Treatment

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences 501 Haike Road Shanghai 201203 China

University of Chinese Academy of Sciences Beijing 100049 China

State Key Laboratory of Drug Research & Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China

China State Institute of Pharmaceutical Industry Shanghai 201203 China

State 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 China

Yantai Institute of Materia Medica Shandong 264000 China

National Facility for Protein Science in Shanghai Zhangjiang Lab Shanghai 201210 China

Yantai Key Laboratory of Nanomedicine & Advanced Preparations Yantai Institute of Materia Medica Shandong 264000 China

School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech University Shanghai 201210 China

Shanghai Clinical Research and Trial Center Shanghai 201203 China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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