Ultrasound‐Activated Piezoelectric Nanoparticles Targeting and Activating NK Cells for Tumor Immunotherapy
Abstract
Abstract Natural killer (NK) cells can swiftly and efficiently kill tumor cells with low toxicity and show great potential as anticancer agents. However, the hostile tumor microenvironment (TME) reduces the number and functionality of NK cells, leading to tumor progression and the limited therapeutic effect of adoptively transferred NK cells, especially in solid tumors. Here, via mussel‐inspired chemistry and targeted antibody modification strategies, functional piezoelectric nanoparticles are designed to target NK cells, named as αCD56‐P@BT (for human) or αNK1.1‐P@BT (for mouse). With external ultrasonic stimulation, αCD56‐P@BT or αNK1.1‐P@BT can enhance the cytotoxicity and cytokine‐producing ability of NK cells. Mechanistically, the synergistic mechanical and electrical signals generated by ultrasound‐irritated P@BT activate the TRP ion channel‐mediated calcium ion influx and cytoskeleton rearrangement, in turn improving NK cell migration, infiltration, and function. Upon transfer therapy, NK cells loaded with αNK1.1‐P@BT exhibit superior antitumor efficacy in mice with subcutaneous melanoma or intrahepatic cholangiocarcinoma under ultrasonic treatment. Moreover, transfer of αCD56‐P@BT loaded NK‐92 cells retard the growth of human hepatoma xenograft in immunodeficient mice. This work establishes a wireless electrostimulation strategy integrating ultrasound‐responsive nanomaterials to potentiate the cytotoxic activity of NK cells, thereby advancing the clinical translation of NK cell adoptive immunotherapy for solid tumors.
Article Details
Authors (14)
Ruitong Zhang
Wenwen Yang
Zhiyuan Zhou
Miaomiao Ding
School of Materials Science and Engineering, Sun Yat-sen University
Hao Wang
Division of Quantitative Sciences, Department of Oncology Johns Hopkins University School of Medicine Baltimore Maryland USA
Wenjing Yuan
Key Laboratory for Experimental Teratology of Ministry of Education Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Basic Medical Sciences Cheeloo Medical College of Shandong University Shandong University Jinan Shandong 250012 China
Renhui Sun
Key Laboratory for Experimental Teratology of Ministry of Education Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Basic Medical Sciences Cheeloo Medical College of Shandong University Shandong University Jinan Shandong 250012 China
Xuetian Yue
Department of Cellular Biology School of Basic Medical Science Cheeloo Medical College of Shandong University Shandong University Jinan Shandong 250012 China
Zhuanchang Wu
Key Laboratory for Experimental Teratology of Ministry of Education Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Basic Medical Sciences Cheeloo Medical College of Shandong University Shandong University Jinan Shandong 250012 China
Chunyang Li
School of Ecology, Environment and Resources, Guangdong University of Technology, Guangzhou, China.
Lifen Gao
Key Laboratory for Experimental Teratology of Ministry of Education Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Basic Medical Sciences Cheeloo Medical College of Shandong University Shandong University Jinan Shandong 250012 China
Chunhong Ma
Hong Liu
Xiaohong Liang
Key Laboratory for Experimental Teratology of Ministry of Education Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology School of Basic Medical Sciences Cheeloo Medical College of Shandong University Shandong University Jinan Shandong 250012 China