(650a) Chiral Supraparticles for Controllable Nanomedicine

Chirality is ubiquitous in nature that is hard-wired into every living biological system. The well-known examples are L- type amino acids and D- type sugars such as DNA and RNA. Since the chirality of building block decides the handedness of assembled structures, proteins such as enzymes are also chiral. A volatile molecule limonene may smell like pine or lemon depends on the handedness of the molecule that reaches to nose. For the same reason, a substrate may or may not be an effective medicine, and makes foods taste bitter or sweet because all receptors in our nose, cells, and tongue in general are chiral and react differently depends on the enantiomer they encounter.

Despite of the critical role, the nexus of chiral bioengineering has not been explored. One of them is lipids in cellular membrane that are all right-handed. Lipids are the major component that decides biophysical properties of cell membrane. Hence lipid composition is the first metabolic change with most of human diseases including metabolic, immune and cancers. It has been well demonstrated that tumor/cancer cells possess increased amount of cholesterol in the cell membrane. When tumor expresses excess amount of cholesterols, it adapts drug resistance because it promotes highly ordered and rigid cell membrane. The design of nanomedicine to overcome this barrier is significantly important for effective drug delivery.

Chiral nanostructures are a sharp tool because cells possess one type of lipid enantiomer in the membrane. It has been well understood that interactions between L- to L- and D- to D- are thermodynamically stronger than L- to D-. Here we designed chiral supraparticles (SPs) that react distinctively to cell membrane depends on their handedness. SPs coordinated with D- chirality showed at least four times stronger cell membrane penetrations and anti-cancer properties. We carried out QCM-D and ITC measurements to understand the mechanism, which confirmed that D- SPs has more effective adhesion on lipid layers than L-SPs. 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 bioengineering. As a result, chiral engineering may have the potential to provide a new level of control for DDS, tumor detection markers, biosensors, and many other biomaterial devices.