posted on 2024-02-26, 12:33authored byXuanbo Zhang, Kaiyuan Wang, Zhiqiang Zhao, Xinzhu Shan, Yuequan Wang, Zunyong Feng, Bingyu Li, Cong Luo, Xiaoyuan Chen, Jin Sun
Tapping
into the innate immune system’s power, nanovaccines
can induce tumor-specific immune responses, which is a promising strategy
in cancer immunotherapy. However, traditional vaccine design, requiring
simultaneous loading of antigens and adjuvants, is complex and poses
challenges for mass production. Here, we developed a tumor nanovaccine
platform that integrates adjuvant functions into the delivery vehicle,
using branched polyguanidine (PolyGu) nanovaccines. These nanovaccines
were produced by modifying polyethylenimine (PEI) with various guanidine
groups, transforming PEI’s cytotoxicity into innate immune
activation. The PolyGu nanovaccines based on poly(phenyl biguanidine
) (Poly-PBG) effectively stimulated dendritic cells, promoted their
maturation via the TLR4 and NLRP3 pathways, and
displayed robust in vivo immune activity. They significantly
inhibited tumor growth and extended mouse survival. The PolyGu also
showed promise for constructing more potent mRNA-based nanovaccines,
offering a platform for personalized cancer vaccine. This work advances
cancer immunotherapy toward potential clinical application by introducing
a paradigm for developing self-adjuvanting nanovaccines.