• 主页
  • 查找结果
  • Cell-Penetrating Nanoparticles Activate the Inflammasome to Enhance Antibody Production by Targeting Microtubule-Associated Protein 1-Light Chain 3 for Degradation.

Cell-Penetrating Nanoparticles Activate the Inflammasome to Enhance Antibody Production by Targeting Microtubule-Associated Protein 1-Light Chain 3 for Degradation.

ACS nano (2020-02-15)
Motao Zhu, Libo Du, Ruifang Zhao, Helen Y Wang, Yuliang Zhao, Guangjun Nie, Rong-Fu Wang
摘要

Engineered nanoparticles could trigger inflammatory responses and potentiate a desired innate immune response for efficient immunotherapy. Here we report size-dependent activation of innate immune signaling pathways by gold (Au) nanoparticles. The ultrasmall-size (<10 nm) Au nanoparticles preferentially activate the NLRP3 inflammasome for Caspase-1 maturation and interleukin-1β production, while the larger-size Au nanoparticles (>10 nm) trigger the NF-κB signaling pathway. Ultrasmall (4.5 nm) Au nanoparticles (Au4.5) activate the NLRP3 inflammasome through directly penetrating into cell cytoplasm to promote robust ROS production and target autophagy protein-LC3 (microtubule-associated protein 1-light chain 3) for proteasomal degradation in an endocytic/phagocytic-independent manner. LC3-dependent autophagy is required for inhibiting NLRP3 inflammasome activation and plays a critical role in the negative control of inflammasome activation. Au4.5 nanoparticles promote the degradation of LC3, thus relieving the LC3-mediated inhibition of the NLRP3 inflammasome. Finally, we show that Au4.5 nanoparticles could function as vaccine adjuvants to markedly enhance ovalbumin (OVA)-specific antibody production in an NLRP3-dependent pattern. Our findings have provided molecular insights into size-dependent innate immune signaling activation by cell-penetrating nanoparticles and identified LC3 as a potential regulatory target for efficient immunotherapy.

材料
货号
品牌
产品描述

Sigma-Aldrich
柠檬酸钠三盐基 二水合物, ACS reagent, ≥99.0%
Sigma-Aldrich
氯化金 (III) 水合物, 99.995% trace metals basis
Sigma-Aldrich
硼氢化钠, purum p.a., ≥96% (gas-volumetric)
Sigma-Aldrich
四辛基溴化铵, 98%
Sigma-Aldrich
金纳米颗粒, 5 nm diameter, biotin terminated, PEG 5000 coated, OD 50, dispersion in H2O
Sigma-Aldrich
Amyloid Protein Non-Aβ Component, ≥80% (HPLC)