OC 56.3 Platelets Transfected with a KRASG12D-Silencing siRNA Reduce Pancreatic Tumor Mass In Vivo in Mice

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by dynamic light scattering, zeta potential (ZP), and fluorescence spectroscopy.Chromogenic substrate and plasma clotting assays were used to study the effects of LPS on FXII activation and FXIIa activity.Results: O111:B4, O26:B6, and Rd2 produced aggregates with hydrodynamic diameters of 123 ± 38, 213 ± 46, 201 ± 42 nm; and ZP of -0.414.2 ± 0.9, -23.0 ± 2.1, -55.0 ± 2.1 mV, respectively.Using pyrene fluorescence, it was determined that the microenvironment within aggregates is most hydrophobic with Rd2.LPS showed procoagulant activity reducing the clotting time from 555 ± 6 seconds to 234 ± 12 for O111:B4, 208 ± 8 for O26:B6, and 280 ± 21 for Rd2.FXII was not activated by O111: B4 or Rd2 but was activated by O26:B6.O26:B6 showed a bell-shaped dose-response curve, suggesting a template mechanism for FXII autoactivation.The amidolytic activity of FXIIa was not affected in the presence of O111:B4, which was corroborated by the calculated values of Vmax and KM.In contrast, FXIIa amidolytic activity was increased in the presence of Rd2 and O26:B6, showing a sigmoidal kinetics curve, indicating a positive allosteric modulation.However, at higher concentrations, FXIIa activity decreased in the presence of O26:B6, which could be a result of protein structural modification and/or steric effects.Conclusion(s): These investigations show that LPS chemotypes specifically impact the activation and activity of FXII, and as such, may differentially respond to therapeutics targeting contact pathway activation.

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