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. 2020 Apr 21:2020:7474807.
doi: 10.1155/2020/7474807. eCollection 2020.

Mechanistic Understanding of Cell Recognition and Immune Reaction via CR1/CR3 by HAP- and SiO2-NPs

Tingting Ding  1 , Jiao Sun  1
Affiliations

Mechanistic Understanding of Cell Recognition and Immune Reaction via CR1/CR3 by HAP- and SiO2-NPs

Tingting Ding et al. Biomed Res Int. .

Abstract

Nanodrug carrier will eventually enter the blood when intravenously injected or in other ways. Meanwhile, a series of toxic effects were caused to the body with the formation of nanoparticle protein corona. In our studies, we try to reveal the recognition mechanism of nanoparticle protein corona by monocyte and the damage effect on immune cells by activated complement of hydroxyapatite nanoparticles (HAP-NPs) and silicon dioxide nanoparticles (SiO2-NPs). So expressions of TLR4/CR1/CR were analyzed by flow cytometry (FCM) in order to illuminate the recognition mechanism of nanoparticle protein corona by monocyte. And the expression of ROS, cytokines, adhesion molecules, and arachidonic acid was measured when THP-1 and HUVECs were stimulated by NP-activated complement. The results showed that HAP-NPs can be recognized by the opsonin receptor (iC3b/CR3) model, while plasma protein, opsonin receptor, and Toll-like receptors are all likely launch cell recognition of SiO2-NPs. And it was considerate that NP-activated complement can damage THP-1 and HUVECs, including oxidative stress, inflammation, and increased vascular permeability. So the surface of nanodrug carrier can be modified to avoid being clear and reduce the efficacy according to the three receptors (TLR4/CR1/CR3).

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Characterization of HAP-NPs and SiO2-NPs. (a) TEM image showing size distribution for HAP-NPs; (b) XRD patterns for HAP-NPs. (c) TEM image showing size distribution for SiO2-NPs; (d) XRD patterns for SiO2-NPs.
Figure 2
Figure 2
Scheme of possible mechanisms of HAP-NPs recognition by THP-1. (1) HAP-NPs-Pro: nanoparticles be deposited of activated complement proteins; (2) HAP-NPs: nanoparticles which were not incubated with human serum and were without adhesive protein on the surface; (3) HAP-C: activated complement supernatant after incubation and centrifuge of nanoparticles and human serum (∗P < 0.05 versus NC group).
Figure 3
Figure 3
Scheme of possible mechanisms of SiO2-NPs recognition by THP-1. (1) SiO2-NPs-Pro: nanoparticles be deposited of activated complement proteins; (2) SiO2-NPs: nanoparticles which were not incubated with human serum and were without adhesive protein on the surface; (3) SiO2-C: activated complement supernatant after incubation and centrifuge of nanoparticles and human serum (∗P < 0.05 versus NC group).
Figure 4
Figure 4
Effect of ROS in THP-1 by activated complement of NPs. (a) For HAP-NPS, HN10: HAP-NPs (10 μg/mL); HD: HAP-NPs/EDTA (0.1 mM EDTA); HG: HAP-NPs/EGTA (1 mM EGTA). (b) For SiO2-NPs, SN6: SiO2-NPs (6 μg/mL); SD: SiO2-NPs/EDTA (0.1 mM EDTA); SG: SiO2-NPs/EGTA (1 mM EGTA). ∗P < 0.05 versus NC group.
Figure 5
Figure 5
Effect of cytokines in THP-1 by activated complement of HAP-NPs. HN10: HAP-NPs (10 μg/mL); HD: HAP-NPs/EDTA (0.1 mM EDTA); HG: HAP-NPs/EGTA (1 mM EGTA). ∗P < 0.05 versus NC group.
Figure 6
Figure 6
Effect of cytokines in THP-1 by activated complement of SiO2-NPs. SN6: SiO2-NPs (6 μg/mL); SD: SiO2-NPs/EDTA (0.1 mM EDTA); SG: SiO2-NPs/EGTA (1 mM EGTA). ∗P < 0.05 versus NC group.
Figure 7
Figure 7
Effect of NF-κB in THP-1 by activated complement of NPs. (a) For HAP-NPs, HN10: HAP-NPs (10 μg/mL); HD: HAP-NPs/EDTA (0.1 mM EDTA); HG: HAP-NPs/EGTA (1 mM EGTA). (b) For SiO2-NPs, SN6: SiO2-NPs (6 μg/mL); SD: SiO2-NPs/EDTA (0.1 mM EDTA); SG: SiO2-NPs/EGTA (1 mM EGTA).
Figure 8
Figure 8
Effect of adhesion molecule in HUVECs by activated complement of NPs: (a) HAP-NPs and (b) SiO2-NPs. ∗P < 0.05 versus NC group.
Figure 9
Figure 9
Effect of cytokines in HUVECs by activated complement of NPs (∗P < 0.05 versus NC group).
Figure 10
Figure 10
Map name of NPs: complement and coagulation cascades (Map ID: ko04610).
See this image and copyright information in PMC

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