Exploring the Heterogeneity of Nanoparticles in Their Interactions with Plasma Coagulation Factor XII.

Abstract

Tuning the characteristics of nanoparticles (NPs) would be promising in improving their biocompatibilities, regarding biosafety and nanodrug considerations. Due to the high priority of the artificial NPs in contacting the circulatory system, understanding their interactions with plasma zymogens is of great importance. Four kinds of NPs, including 5 nm gold NPs (GNP-5), 5 and 20 nm silver NPs (SNP-5, SNP-20), and 20 nm silica NPs (SiNP-20), were investigated for their interactions with the coagulation factor XII (FXII). GNP-5 adsorbed FXII in a standing-up mode, and exhibited high binding affinity for the heavy chain of the protein without altering its secondary structure or inducing its activation. In contrast to GNP-5, FXII adsorption on the other tested NPs was in a lying-down mode, and their interactions with FXII induced its conformational changes, thus causing the evident zymogen cleavage. The structural alterations and activation of FXII induced by the NPs exhibited in specific surface area dependent manners, which were related with different NP cores and sizes. Additionally, the enzymatic activity of α-FXIIa was also influenced by NP incubation, and the alterations were dependent on the specific characters of the NPs as evidenced by the enzymatic inhibition effect of GNP-5 (noncompetitive) and SNP-5 (competitive), and enhanced enzymatic catalysis abilities of SNP-20 and SiNP-20. The interesting findings on the heterogeneity of NPs in their interactions with plasma FXII not only revealed the underlying mechanism for NP-triggered hematological responses, but also suggested the crucial role of tuning NP parameters in their potential bioapplication, like nanodrug design.