Insights into nanoparticle surface bonding and coating architecture via multinuclear NMR

Tantalum oxide nanoparticles (TaO_x NPs) are promising as high-<i>Z</i>-contrast agents for computed tomography (CT) due to their profound imaging benefits relative to those of clinical iodinated contrast media (ICM) at the X-ray tube voltages ≥100 kVp required for most patients. Furthermore, TaO_x NPs have prevailed through extensive non-GLP and GLP (good laboratory practice) preclinical development, including in vivo/vitro safety testing and imaging efficacy studies. This is due in part to innovative structural engineering of the NPs' core size and coating, which has been shown to provide favorable pharmacokinetics and promote rapid renal clearance, with negligible organ retention. In this study, a carboxybetaine zwitterionic siloxane polymer (CZ) coating for a lead candidate TaO_x NP is thoroughly characterized using multinuclear/multidimensional nuclear magnetic resonance (NMR) spectroscopic techniques. ¹H and ¹H/¹³C heteronuclear multiple bond correlation NMR spectroscopies are used to confirm the CZ coating's structure, and in combination with ²⁹Si NMR, the architecture of the siloxane coating bound to the TaO_x NPs' surface is described. Of particular significance, ²⁹Si NMR spectra were used to identify the T-region bonding modes of the CZ coating and show the superiority of diafiltration over dialysis for purification of the TaO_x NPs. Through a spectral comparison, a cyclic siloxane impurity in the TaO_x NP product purified through dialysis was found to be absent in the product purified through diafiltration. Finally, the ¹H Carr-Purcell-Meiboom-Gill (CPMG) NMR pulse sequence was used in a novel manner to probe the distance-dependent interactions between the ¹H spins of the CZ coating and the TaO_x NPs' surface.