Details

Autor(en) / Beteiligte

• Sun, Zhihong
• Sun, Zhuokai
• Liu, Jie
• Gao, Xiaohan
• Jiao, Liping
• Zhao, Qi
• Chu, Yongli
• Wang, Xiaozhong
• Deng, Guanjun
• Cai, Lintao

Titel

Engineered Extracellular Vesicles Expressing Siglec‐10 Camouflaged AIE Photosensitizer to Reprogram Macrophages to Active M1 Phenotype and Present Tumor‐Associated Antigens for Photodynamic Immunotherapy

Ist Teil von

• Small (Weinheim an der Bergstrasse, Germany), 2024-03, Vol.20 (12), p.e2307147-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2024

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Cancer immunotherapy has attracted considerable attention due to its advantages of persistence, targeting, and ability to kill tumor cells. However, the efficacy of tumor immunotherapy in practical applications is limited by tumor heterogeneity and complex tumor immunosuppressive microenvironments in which abundant of M2 macrophages and immune checkpoints (ICs) are present. Herein, two type‐I aggregation‐induced emission (AIE)‐active photosensitizers with various reactive oxygen species (ROS)‐generating efficiencies are designed and synthesized. Engineered extracellular vesicles (EVs) that express ICs Siglec‐10 are first obtained from 4T1 tumor cells. The engineered EVs are then fused with the AIE photosensitizer‐loaded lipidic nanosystem to form SEx@Fc‐NPs. The ROS generated by the inner type‐I AIE photosensitizer of the SEx@Fc‐NPs through photodynamic therapy (PDT) can convert M2 macrophages into M1 macrophages to improve tumor immunosuppressive microenvironment. The outer EV‐antigens that carry 4T1 tumor‐associated antigens directly stimulate dendritic cells maturation to activate different types of tumor‐specific T cells in overcoming tumor heterogeneity. In addition, blocking Siglec‐10 reversed macrophage exhaustion for enhanced antitumor ability. This study presents that a combination of PDT, immune checkpoints, and EV‐antigens can greatly improve the efficiency of tumor immunotherapy and is expected to serve as an emerging strategy to improve tumor immunosuppressive microenvironment and overcome immune escape. SEx@Fc‐NPs are formed by fusing engineered extracellular vesicles with aggregation‐induced emission (AIE) photosensitizer‐loaded lipidic nanoendoskeleton. The inner type‐I AIE photosensitizer can convert M2 macrophages into M1 for improving tumor immunosuppressive microenvironment. The outer EV‐antigens are derived from engineered 4T1 cells that directly stimulated dendritic cells maturation to activate different kinds of tumor‐specific T cells, while blocking Siglec‐10 reversed macrophage exhaustion for improving antitumor.