Gastric cancer is among the most prevalent and lethal malignancies worldwide. Approximately 17-20% of gastric cancer cases exhibit overexpression of human epidermal growth factor receptor 2 (HER2), and HER2-targeted antibody combined with chemotherapy remains a standard treatment strategy. However, acquired resistance significantly limits long-term therapeutic benefits, highlighting the need for innovative treatment approaches.
Natural killer (NK) cells are effective immune effectors capable of rapidly eliminating tumor cells without prior antigen sensitization. However, in solid tumors, NK cells often become dysfunctional due to poor infiltration and immunosuppressive tumor microenvironments, resulting in reduced antitumor activity. Therefore, strategies capable of efficiently redirecting and activating endogenous NK cells represent an important approach for cancer immunotherapy development.
A research team led by Dr. Yinghong Shi and Professor Zhimin Tao and the collaborators at Jiangsu University recently developed a novel bispecific cellular nanovesicle (NV) platform to enhance NK cell-mediated tumor immunity. The study was published in Nano Research on July 22, 2026 under the title “Bispecific cellular nanovesicles potentiate NK cell immunity against gastric cancer.”
The team genetically engineered HEK293 cells to express fusion proteins containing anti-CD16 and anti-HER2 single-chain variable fragments (scFvs). These modified cells were subsequently processed through mechanical extrusion to generate αCD16/αHER2 nanovesicles displaying dual targeting ligands on their surfaces. The resulting nanovesicles were designed to simultaneously recognize CD16 receptors on NK cells and HER2 molecules on gastric cancer cells, thereby bridging immune effector cells and tumor cells.
Comprehensive material characterization demonstrated successful generation of the engineered nanovesicles. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Western blotting, and nanoflow cytometry confirmed that the vesicles possessed typical nanoscale vesicle morphology, stable physicochemical properties, and expression of the engineered targeting proteins. The αCD16/αHER2 nanovesicles showed an average size of approximately 120 nm and retained characteristic extracellular vesicle markers.
Functional studies showed that the bispecific nanovesicles effectively promoted interactions between NK cells and HER2-positive gastric cancer cells. Compared with control nanovesicles, αCD16/αHER2 NVs enhanced NK cell recruitment, stimulated secretion of immune cytokines including IFN-γ and TNF-α, increased CD107a-associated degranulation, and promoted selective killing of HER2-positive gastric cancer cells.
The therapeutic potential of this platform was further validated in vivo using human NK cell-reconstituted mouse models bearing HER2-positive gastric cancer xenografts. Treatment with αCD16/αHER2 NVs resulted in enhanced tumor accumulation, increased NK cell activity within tumors, and significant inhibition of tumor growth without obvious systemic toxicity. These findings demonstrate that engineered cellular nanovesicles can serve as artificial immune regulators to amplify endogenous NK cell responses against solid tumors.
“By integrating biomimetic nanotechnology with immune cell regulation, this study provides a new approach for overcoming limitations associated with current NK cell therapies and bispecific antibody strategies,” said Professor Zhimin Tao, senior author of the study. The developed αCD16/αHER2 nanovesicle platform may provide a versatile strategy for future cancer immunotherapy applications beyond gastric cancer.
The study was conducted by researchers from Jiangsu University, including Yinghong Shi, Wenting Zhang, Xinyang Zhang, Xu Zhang, Xiaojun Shen, Hui Qian, and Zhimin Tao. Professor Tao’s research team focuses on nanomedicine, tumor immunotherapy, sepsis treatment, and translational medicine. The group is currently recruiting postdoctoral researchers in sepsis research, with projects involving sepsis mechanisms, animal models, anti-sepsis drug evaluation, immune regulation, and clinical translation.
DOI Link:
https://doi.org/10.26599/NR.2026.94909052
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 8,000 articles. In 2025 InCites Journal Citation Reports, its 2025 IF is 9.4 (8.3, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.
Nano Research
Engineered nanovesicles enhance natural killer cell immunity against HER2-positive gastric cancer
22-Jul-2026