M1-macrophage membrane-camouflaged nanoframeworks activate multiple immunity via calcium overload and photo-sonosensitization

Yinjing Shen; Nuo Yu; Wenjing Zhao; Shining Niu; Pu Qiu; Haiyan Zeng; Zhigang Chen; Wei Men; Dong Xie

doi:10.1016/j.biomaterials.2025.123287

M1-macrophage membrane-camouflaged nanoframeworks activate multiple immunity via calcium overload and photo-sonosensitization

Biomaterials. 2025 Sep:320:123287. doi: 10.1016/j.biomaterials.2025.123287. Epub 2025 Mar 24.

Authors

Yinjing Shen¹, Nuo Yu¹, Wenjing Zhao¹, Shining Niu¹, Pu Qiu¹, Haiyan Zeng¹, Zhigang Chen², Wei Men³, Dong Xie⁴

Affiliations

¹ State Key Laboratory of Advanced Fiber Materials, Institute of Functional Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China.
² State Key Laboratory of Advanced Fiber Materials, Institute of Functional Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China. Electronic address: zgchen@dhu.edu.cn.
³ State Key Laboratory of Advanced Fiber Materials, Institute of Functional Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China. Electronic address: wenmei@dhu.edu.cn.
⁴ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China. Electronic address: xiedong@tongji.edu.cn.

PMID: 40147112
DOI: 10.1016/j.biomaterials.2025.123287

Abstract

Immunotherapy is a powerful weapon for inhibiting tumor metastasis, while its efficacy is significantly compromised in immunosuppressive tumor microenvironment (TME). To reverse TME, this work has developed biomimetic nanoframeworks with calcium overload and photo-sonosensitization capacity to activate multiple immunities for metastasis inhibition. The biomimetic nanoframeworks were prepared by the assembly of Ca²⁺ ions and Protoporphyrin IX (PpIX) into nanoframeworks (Ca-PpIX), and the encapsulation of M1 macrophage membrane (Ca-PpIX@M). They exhibit pH-dependent Ca²⁺ ions release, ¹O₂ generation and photothermal conversion under external near-infrared light and ultrasound stimuli. The Ca²⁺-overload and elevated ¹O₂ cause oxidative stress within cells, leading to efficient mitochondrial dysfunction. Successively, the mitochondrial dysfunction induces a reduction in adenosine triphosphate (ATP) levels to inhibit the HSP90 expression, improving photothermal ablation's efficacy. The photo-sonosensitization has the ability to repolarize macrophages with the ratio of M1/M2 macrophage increasing from 0.25 to 2.45, which is better than monoactivation. Importantly, the Ca-PpIX@M also can induce the process of immunogenic cell death, resulting in the maturation of dendritic cells (30.2 %) and activation of cytotoxic (12.4 %) and helper T cells (19.7 %), thereby enhancing antitumor immunity in vivo. As a result, tumor growth and metastasis have been significantly inhibited. This work offers insights into developing biomimetic nanoframeworks to reverse TME for activating multiple immunity.

Keywords: Calcium overload; Immunotherapy; M1 nanovesicles; Macrophage re-polarization.

MeSH terms

Animals
Biomimetic Materials / chemistry
Calcium* / metabolism
Cell Membrane* / metabolism
Immunotherapy / methods
Macrophages* / cytology
Macrophages* / immunology
Macrophages* / metabolism
Mice
Mice, Inbred BALB C
Mitochondria / metabolism
Protoporphyrins / chemistry
RAW 264.7 Cells
Tumor Microenvironment

Substances

Calcium
protoporphyrin IX
Protoporphyrins