期刊
NANO LETTERS
卷 22, 期 7, 页码 2978-2987出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c00185
关键词
tumor nanovaccines; nanoadjuvants; Toll-like receptor agonists; hierarchical-responsive nanoparticles
类别
资金
- National Key Research and Development Program of China [2017YFA0205600]
- National Natural Science Foundation of China (NSFC) [81973260, 81903554]
- Beijing Natural Science Foundation [JQ19025]
This study reports a pH-/enzyme-responsive TLR7/8 agonist-conjugated nanovaccine (TNV) that intelligently responds to the endosomal environment and releases the TLR7/8 agonist precisely at the receptor site, resulting in effective immune activation.
Toll-like receptor (TLR) agonists are potent immune-stimulators that hold great potential in vaccine adjuvants as well as cancer immunotherapy. However, TLR agonists in free form are prone to be eliminated quickly by the circulatory system and cause systemic inflammation side effects. It remains a challenge to achieve precise release of TLR7/8 agonist in the native form at the receptor site in the endosomal compartments while keeping stable encapsulation and inactive in nontarget environment. Here, we report a pH-/enzyme-responsive TLR7/8 agonist-conjugated nanovaccine (TNV), which responds intelligently to the acidic environment and cathepsin B in the endosome, precisely releases TLR7/8 agonist to activate its receptor signaling at the endosomal membrane, stimulates DCs maturation, and provokes specific cellular immunity. In vivo experiments demonstrate outstanding prophylactic and therapeutic efficacy of TNV in mouse melanoma and colon cancer. The endosome-targeted responsive nanoparticle strategy provides a potential delivery toolbox of adjuvants to advance the development of tumor nanovaccines.
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