Programmable nanomotor system responsively and chemotactically captures tumor associated antigens for enhanced in situ cancer vaccine

  • Mater Today Bio. 2025 Nov 11:35:102543. doi: 10.1016/j.mtbio.2025.102543.
Panpan Song  1  2  3 ,  Xiaoqing Han  2 ,  Yanjing Wang  1  2  3 ,  Xingbo Wang  4 ,  Yaqing Kang  2 ,  Jiao Yan  1  4 ,  Haiyuan Zhang  1  4
Affiliations
  • 1. The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China.
  • 2. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
  • 3. School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, China.
  • 4. School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, 511436, China.
PMID: 41322135 DOI: 10.1016/j.mtbio.2025.102543
Abstract

In situ Cancer vaccines that utilize the body's own tumor-associated antigens (TAAs) to induce tumor-specific adaptive immune responses are emerging as a promising strategy in Cancer therapy. However, the rapid clearance of TAAs due to innate immune system hinders the development of effective antitumor immunity. To address this challenge, we developed a nanomotor system (DDMSN@MOMVPF) as an in situ Cancer vaccine capable of chemotactically capturing TAAs, significantly inhibiting the rapid clearance of TAAs and enhancing Cancer Immunotherapy. In response to acid tumor microenvironment, DDMSN@MOMVPF exfoliated folate acid-attached, mitoxantrone-embedded Bacterial outer membrane vesicle (OMV) fragments, which could be specifically taken up by tumor cells to induce immunogenic cell death (ICD) and release DNA-associated TAAs. Subsequently, the exposed DNase on DDMSN@MOMVPF detected DNA gradient and propelled nanoparticles chemotactically capturing TAAs. In vivo results indicated that DDMSN@MOMVPF suppressed both primary and distant tumors and elicited immune memory effects to prevent tumor recurrence.

Keywords
Cancer immunotherapy; Dendritic mesoporous silica nanoparticles; Nanomotors; Outer membrane vesicles; TAA capture.
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