Center for Self-assembly and Complexity

5. Chemotherapy Submarine Circulating in the Blood

Cancer is one of the final targets to be overcome in modern medicine. Even though a variety of anticancer drugs have been developed for a long time, an effective treatment by anticancer drugs is still far-off. However, our group has presented a breakthrough in cancer treatment. Group leader Won Jong Kim has successfully developed a new concept for an anticancer drug delivery system using polymer and Host-Guest Chemistry. The focus of this study is to develop a “Drug Delivery Carrier” for minimizing the side effects as well as delivering drugs only to specific cancer cells. Unlike conventional micelles, polymerized host and guest molecules on the polymer can be easily synthesized and the resultant polymerized host-guest interaction has a strong binding force, which leads to a safe and selective delivery of drugs to cancer cells.

The field for studying the host-guest relationship is called the “Host-Guest Chemistry.” In this field, the specific interaction between host molecules and guest molecules enables us to separate specific material or to develop a new structure. The interaction between host molecules and guest molecules occurs by hydrogen bonds, ionic bonds, van der Waals forces and hydrophobic interactions rather than by general covalent bonds.
The host molecule is a ringshaped compound, such as cucurbit[n]uril, calixarene and pillararene other than the cyclodextrin that was used in this study. This figure shows a typical host-guest interaction between the typical host-molecule, ß-cyclodextrin and the typical guest-molecule, paclitaxel.

As the CD acts like a host, the anticancer drug PTX as a guest enters the empty space in the center of a ring-type sugar, CD. To trigger the efficient delivery of nano-assembly into the cytoplasm, the target peptide (AP-1: CRKRLDRNC), which is the ligand for interleukin-4 (IL-4) receptor on the cell membrane, is conjugated to the pPTX polymer, one of the building blocks of the nano-assembly. In order to improve the host-guest interactions and delivery efficiency, cyclodextrin (CD) and Paclitaxel (PTX) are conjugated to the polymer, forming pCD and pPTX, respectively. poly(MAnh) (Poly(Maleic anhydride)) is used to polymerize the CD and PTX. Through the reaction between the hydroxyl groups of the CD and the PTX (red and green dashed circles, respectively) and the MAnh groups, CD and PTX were conjugated to the polymer by ester bonding. The host-guest interactions between the pCD and the pPTX produce the AP-1-pPTX/pCD nano-assembly. This nano-assembly maintains its stability in the blood due to a strong host-guest interaction resulting from polymerization. In the cytoplasm, the nano-assembly is degraded by esterases. As a result, the PTX is separated and then released. The released PTX induces the apoptosis of cancer cells.

Namgung, R.; Lee, Y. M.; Kim, J.; Jang, Y.; Lee, B.-H.; Kim, I.-S.; Sokkar, P.; Rhee, Y. M.; Hoffman, A. S.; Kim, W. J. “Poly-cyclodextrin and Poly-paclitaxel Nano-assembly for Anticancer Therapy” Nature Comm. 2014, 5, 3702.