Chirality engineering of supraparticles for controllable nanomedicine

Abstract

Chirality is ubiquitous in nature that is hard-wired into every living biological system. Despite of the critical role, the nexus of chirality engineering on biomaterials has not been explored. Here we designed chiral supraparticles (SPs) that react distinctively to cells and proteins depending on their handedness. SPs coordinated with D- chirality showed at least three times more efficient cell membrane penetrations and anti-cancer properties. We carried out quartz crystal microbalance with dissipation (QCM-D) and isothermal titration calorimetry (ITC) measurements to understand the mechanism, which confirmed that D-SPs had more effective adhesion on lipid layers where most of phospholipids in nature has D-chirality. The stronger affinity of D-SPs over L-SPs to lipids was because interactions between D- to D- are thermodynamically more stable than that of D- to L-. When it comes to in vivo environments that contains a large, heterogeneous population of proteins, D-SPs showed superior stability and longer biological half-lives due to the incompatible chirality with endogenous proteins including proteases. This study shows that incorporating D-chirality into nanosystems enhances cellular uptake and in vivo stability in blood providing support for the importance of chirality in biomaterials. Chirality engineering will provide “smart” platforms for drug delivery systems, tumor detection markers, biosensors, and many other biomaterial devices.