He Ao, Li Qiang, Dang Meng, Lu Wei, Li Xiaoye, Dai Zhuo, Ding Meng, Zhang Yu, Dong Heng, Teng Zhaogang, Mou Yongbin
Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, 30 Zhongyang Road, Nanjing, Jiangsu, 210008, China.
Key Laboratory for Organic Electronics and Information Displays, Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing, Jiangsu, 210023, China.
Adv Healthc Mater. 2024 Dec;13(31):e2401199. doi: 10.1002/adhm.202401199. Epub 2024 Jul 25.
The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8 and CD4 T cells targeting specific antigens, reducing immunosuppression by regulatory T cells, and boosting the populations of effector memory T cells. These findings underscore that the simple yet potent strategy of employing minimal flexible nanocapsules markedly enhances DC-mediated antitumor immunotherapy, offering promising avenues for future clinical applications.
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