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Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.
Xiong, Hongjie; Song, Zhongquan; Wang, Tingya; Huang, Ke; Yu, Fangfang; Sun, Wenyu; Liu, Xiaohui; Liu, Liu; Jiang, Hui; Wang, Xuemei.
Afiliação
  • Xiong H; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China.
  • Song Z; Department of Respiratory Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China.
  • Wang T; Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, PR China.
  • Huang K; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China.
  • Yu F; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China.
  • Sun W; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China.
  • Liu X; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China.
  • Liu L; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China. Electronic address: liuliux@seu.edu.cn.
  • Jiang H; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China. Electronic address: sungi@seu.edu.cn.
  • Wang X; State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, PR China. Electronic address: xuewang@seu.edu.cn.
Biomaterials ; 312: 122712, 2025 Jan.
Article em En | MEDLINE | ID: mdl-39098305
ABSTRACT
Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fotoquimioterapia / Fármacos Fotossensibilizantes / MicroRNAs / Microambiente Tumoral / Neoplasias de Mama Triplo Negativas / Lipossomos Limite: Animals / Female / Humans Idioma: En Revista: Biomaterials Ano de publicação: 2025 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fotoquimioterapia / Fármacos Fotossensibilizantes / MicroRNAs / Microambiente Tumoral / Neoplasias de Mama Triplo Negativas / Lipossomos Limite: Animals / Female / Humans Idioma: En Revista: Biomaterials Ano de publicação: 2025 Tipo de documento: Article