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A human endogenous protein exerts multi-role biomimetic chemistry in synthesis of paramagnetic gold nanostructures for tumor bimodal imaging

Yang, Weitao, Wu, Xiaoli, Dou, Yan, Chang, Jin, Xiang, Chenyang, Yu, Jiani, Wang, Jun, Wang, Xiuli, Zhang, Bingbo
Biomaterials 2018 v.161 pp. 256-269
Monte Carlo method, T-lymphocytes, X-radiation, adsorption, amino acid motifs, biocompatibility, biomimetic synthesis, biomimetics, chelating agents, crystallization, gadolinium, glutathione transferase, gold, humans, image analysis, immune response, ions, moieties, nanogold, nanoparticles, neoplasms, pharmacokinetics, proteins, reducing agents, temperature, toxicity
Protein-mediated biomimetic nanoparticles because of simplicity of their synthesis, subdued nonspecific adsorption, improved pharmacokinetics, and biocompatibility have been receiving increasing attention recently. Nevertheless, only a handful of proteins have been developed for biomimetic synthesis. Worse still, most of them are constrained on single-function usages in chemistry. Exploring new functional proteins, especially those with multi-dentate moieties for multi-role biomimetic chemistry, still remains a substantial challenge. Here, we report on a human endogenous protein, glutathione S-transferase (GST), with favorable amino acid motifs, that has innate talents in incubating high quality gold nanoparticles without adding reducing agents at physiological temperature, and particularly can further anchor gadolinium ions without adding extra chelators. The resultant paramagnetic AuNPs@GSTGd exhibits highly crystallization and uniform size of ca. 10 nm. Compared with clinical contrast agents (Iopamidol, Magnevist), AuNPs@GSTGd shows better imaging performance (e.g. enhanced relaxivity and larger X-ray attenuation efficiency) with clear evidence from Monte Carlo simulation and in vitro experimental results. Further in vivo imaging demonstrates good tumor targeting and clearance of AuNPs@GSTGd without obvious systemic toxicity. Particularly, low immunogenicity of AuNPs@GSTGd is certified by immunological status evaluation of T cells after stimulated with them. This study for the first time demonstrates the manipulation of a human protein for multi-role biomimetic chemistry depending on its unique amino acid motifs and its incorporation into a synthetic agent for potentially addressing some critical issues in cancer nanotheranostics such as synthetic methodology, biocompatibility, function integration, targeting, and immunogenicity.