Homologous-targeting biomimetic nanoparticles co-loaded with melittin and a photosensitizer for the combination therapy of triple negative breast cancer.
Tao Zhang, Liya Bai, Ran You, Meng Yang, Qian Chen, Yuanyuan Cheng, Zhanyin Qian, Yinsong Wang, Yuanyuan Liu
Author Information
Tao Zhang: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Liya Bai: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Ran You: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Meng Yang: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Qian Chen: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Yuanyuan Cheng: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Zhanyin Qian: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn.
Yinsong Wang: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn. ORCID
Yuanyuan Liu: Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. liuyuanyuan01@tmu.edu.cn. ORCID
Melittin (Mel) is considered a promising candidate drug for the treatment of triple negative breast cancer (TNBC) due to its various antitumor effects. However, its clinical application is hampered by notable limitations, including hemolytic activity, rapid clearance, and a lack of tumor selectivity. Here, we designed novel biomimetic nanoparticles based on homologous tumor cell membranes and poly(lactic--glycolic acid) (PLGA)/poly(beta-aminoester) (PBAE), denoted MDM@TPP, which efficiently coloaded the cytolytic peptide Mel and the photosensitizer mTHPC. Both and , the MDM@TPP nanoparticles effectively mitigated the acute toxicity of melittin and exhibited strong TNBC targeting ability due to the homologous targeting effect of the tumor cell membrane. Under laser irradiation, the MDM@TPP nanoparticles showed excellent photodynamic performance and thus accelerated the release of Mel by disrupting cell membrane integrity. Moreover, Mel combined with photodynamic therapy (PDT) can synergistically kill tumor cells and induce significant immunogenic cell death, thereby stimulating the maturation of dendritic cells (DCs). In 4T1 tumor-bearing mice, MDM@TPP nanoparticles effectively inhibited the growth and metastasis of primary tumors and finally prevented tumor recurrence by improving the immune response.
