4.5 Article

A simple self-adjuvanting biomimetic nanovaccine self-assembled with the conjugate of phospholipids and nucleotides can induce a strong cancer immunotherapeutic effect

期刊

BIOMATERIALS SCIENCE
卷 9, 期 1, 页码 84-92

出版社

ROYAL SOC CHEMISTRY
DOI: 10.1039/d0bm01333a

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资金

  1. Natural Science Foundation of China [31870920]
  2. CAMS Innovation Fund for Health and Longevity Pilot Project (Youth Award Program) [2019-RC-HL-015]
  3. CAMS Innovation Fund for Medical Sciences [CAMS-I2M-3-004]

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The study developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which effectively stimulated antigen responses, provided sustained antigen supply, induced CD8(+) T-cell responses, and showed significant anti-tumor effects and survival prolongation. This nanovaccine self-assembled with phospholipid-nucleotide amphiphiles offers a safe, simple, and efficient approach for anti-tumor immunotherapy.
Biomimetic nanoparticles have potential applications in many fields due to their favorable properties. Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthesized with the phospholipids of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and hydrophilic Toll-like receptor (TLR9) agonist CpG ODN. The nanovaccine could not only provide effective initial antigen stimulation and sustained long-term antigen supply with a controlled release, but also induce antigen cross-presentation via the MHC-I pathway initiating CD8(+) T-cell responses. Moreover, the dense nucleotide shell around the nanovaccine could promote antigen endocytosis via various receptor-mediated pathways into dendritic cells. CpG ODN interacted with TLR9 triggering the cytokine secretion of TNF-alpha and IL-10, which further boosted the anti-tumor humoral and cellular immune responses, which led to a significant tumor suppressive effect and remarkable survival prolongation. So, this nanovaccine self-assembled with phospholipid-nucleotide amphiphiles can serve as a safe, simple and efficient approach for anti-tumor immunotherapy.

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