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. Author manuscript; available in PMC: 2023 Jan 17.
Published in final edited form as: Mol Pharm. 2020 Sep 2;17(10):3900–3914. doi: 10.1021/acs.molpharmaceut.0c00641

Table 2.

Key Findings Associated with the Acute Immunogenicity Studies

immunogenicity study key findings
effect of particle size and dose •mean concentrations of IL-6, IL-10, TNF-α, and MCP-1 in blood serum, the liver, and the spleen were significantly lower than the corresponding LPS-induced concentrations at all investigated μNET relative doses
•although there were some increases in the mean concentrations of IL-6, IL-10, TNF-α, and MCP-1 relative to those induced by PBS, in general, they did not appear to correlate with the investigated μNET doses, possibly because of the variabilities in response among animals
•mean concentrations of IL-6 in blood serum, the liver, and the spleen in response to the investigated nNET doses were significantly belowLPS-induced concentrations
• 1× nNETs induced significantly higher concentrations of TNF-α as compared to 0.5× nNETs and 0.25× nNETs in blood serum, the liver, and the spleen
•all investigated nNET doses induced significantly higher concentrations of MCP-1 in the liver and spleen as compared to PBS
•mean concentrations of IL-6 and IL-10 in blood serum, the liver, and the spleen did not significantly change at 2, 4, and 6 h postinjection of either 1× μNETs or 1× nNETs
•mean concentrations of TNF-α and MCP-1 in blood serum did not significantly change at 2, 4, and 6 h postinjection of 1× μNETs
•mean concentrations of TNF-α and MCP-1 in the liver were significantly higher at 4 and 6 h postinjection of 1× μNETs as compared to their corresponding values at 2 h
time-dependent cytokine response •mean concentration of MCP-1 in the spleen at 4 and 6 h postinjection of 1× μNETs was significantly higher than its respective concentration at 2 h, and at all three time points, the 1× μNETs induced significantly higher levels of McP-1 as compared to PBS
•mean concentrations of TNF-α in blood serum, the liver, and the spleen at 6 h postinjection of 1× nNETs were significantly lower than their respective concentrations at 2 h
•mean concentrations of MCP-1 in the liver and spleen at 6 h postinjection of 1× nNETs were significantly lower than their respective concentrations at 2 h, but not significantly different from PBS-induced MCP-1 concentration in the liver at 6 h
effects of nNET functionalization with folate or Herceptin •functionalization of nNETs was associated with a general trend in reduction of IL-6 and MCP-1 concentrations in blood serum, the liver, and the spleen, and TNF-α and IL-10 concentration reduction in blood serum
effects of dual injections one week apart •with the exception of IL-10 in the spleen in response to nNETs, the second injection of 0.5× μNETs or 0.5× nNETs did not result in statistically significant changes in concentrations of other cytokines as compared to a single injection