Natural killer (NK) cells can rapidly and efficiently kill tumor cells with low toxicity and have shown great potential as anticancer agents. However, the malignant tumor microenvironment (TME) reduces the number and function of NK cells, leading to tumor progression, and the therapeutic effect of transferred NK cells is limited, especially in solid tumors. Here, through mussel-inspired chemical and targeted antibody modification strategies, functional piezoelectric nanoparticles were designed to target NK cells, referred to as αCD56-P@BT (human) or αNK1.1-P@BT (mouse).Functional piezoelectric nanoparticles are designed to target NK cells, referred to as αCD56-P@BT (human) or αNK1.1-P@BT (mouse). Through external ultrasound stimulation, αCD56-P@BT or αNK1.1-P@BT can enhance the cytotoxicity and cytokine production of NK cells. Mechanistically, the synergistic mechanical and electrical signals generated by ultrasound-stimulated P@BT activate TRP ion channel-mediated calcium influx and cytoskeletal rearrangement, thereby improving NK cell migration, infiltration, and function.In adoptive transfer therapy, NK cells carrying αNK1.1-P@BT demonstrate superior antitumor efficacy in mice with subcutaneous melanoma or intrahepatic cholangiocarcinoma. In addition, the transfer of NK-92 cells carrying αCD56-P@BT slows the growth of human liver cancer xenografts in immunodeficient mice. This study established a radio-stimulation strategy that, combined with ultrasound-responsive nanomaterials, enhances the cytotoxic activity of NK cells, thereby advancing the clinical translation of NK cell-based immunotherapy for solid tumors.

Original link

Pub Date : 2025-09-07

DOI: 10.1002/adma.202508101

Ruitong Zhang,  Wenwen Yang,  Zhiyuan Zhou,  Miaomiao Ding,  Hao Wang,  Wenjing Yuan,  Renhui Sun,  Xuetian Yue,  Zhuanchang Wu,  Chunyang Li,  Lifen Gao,  Chunhong Ma ,  Hong Liu,  Xiaohong Liang