Optimizing a novel Au-grafted lipid nanoparticle through chelation chemistry for high photothermal biologic activity

Abstract Gold nanoparticles through nucleation of Au clusters have been extensively studied. However, due to low potency, prolonged tissue retention and irreversible accumulation, the safety considerations have limited their therapeutic and diagnostic applications. Novel gold nanostructures with retained physical properties and higher biodegradability could be prepared by alternative approaches. Previously, a lipid nanoparticle (LNP) platform carrying gadolinium (Gd3+) has been reported to eliminate through the biliary without accumulation in the liver or kidney within 24 hrs1. Inspired by this discovery, we investigated a new approach of forming gold nanoparticles using preformed LNPs grafting DTPA (diethylenetriamine-pentaacetic acid) as chelating agent. Tiny Au nanoparticles are formed by simply mixing Au3+ with preformed DTPA-LNP. The Au3+ associates stably to these LNPs after a systematic optimization. The Au-LNPs are scalable and showed excellent photothermal effects when subjected to near-infrared light irradiation. They exhibit enhanced light-induced tumor cell killing at higher efficiency, compared to that of classical gold nanoparticles (citrated reduced). Given an additional small dose (2 Gy) of gamma irradiation, Au-LNPs could produce synergistic photothermal and radiotherapeutic effects under reduced light dose. The simple and adaptive nanoparticle design may enhance the margin of safety of gold nanoparticles in the treatment of cancers and other diseases.