Dr. Jungkyun Im has obtained his Ph.D. degree in 2010 from Pohang university of science and technology in the field of bioorganic medicinal chemistry. During the Ph.D. course he has synthesized glycodendrimer, molecular transporter, stereoisomers of kinase inhibitor, and etc. In particular, to overcome the problems in the drug delivery across biological barriers, he prepared a series of novel molecular transporters based on carbohydrate as a scaffold. The G8 (containing eight guanidine units) sorbitol-based molecular transporter was found to be highly effective in cellular uptake as well as crossing the BBB. Employing the G8 sorbitol-based molecular transporter, he has prepared AZT(the first drug approved by FDA for the treatment of AIDS), and 5-Fu(the drug approved for the treatment of solid tumors) conjugates to examine their delivery to the mouse brain.
The blood brain barrier (BBB) is composed of densely packed endothelial cells which surrounds the vessels of the brain. Endothelial cells of brain capillaries are tightly joined through tight junctions. Thus most molecules in blood plasma such as chemicals as well as pathogens are excluded from the brain. Due to this unique barrier property, brain can be effectively protected from common infectious and inflammatory processes. On the other hand, when the brain is in trouble by a certain disease, the BBB becomes the major hurdle for drug delivery to the brain. In addition, many kinds of efflux pumps are present in the endothelial cells in the brain. For these reasons, the development of CNS (central nervous drug) drugs with the BBB permeability is the major issue in pharmaceutical research. Employing the G8 sorbitol-based molecular transporter, we have prepared AZT and 5-FU conjugates to examine their delivery to the mouse brain. The transporter has two selectively protected-primary hydroxyl groups. One hydroxyl group was conjugated to the drug of interest, while the other was used to attach a fluorophore via suitable linkers. For AZT and 5-FU conjugation, we utilized the succinate ester linker, which can be enzymatically cleaved to release the drug after successful delivery to tissues.
Nan Qin is an Assistant Professor of State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology (SIMIT), Chinese Academy of Sciences (CAS). He obtained his PhD in Condensed Matter Physics from Shanghai University in 2014. After this, he joined SIMIT. His research activities focus on eco-friendly nanofabrication, near-filed infrared nanocharacterization of biomaterials (such as natural silkworm protein and genetic engineering synthesized spider silk protein) and applications of protein based micro/nano devices in bio-sensing and biomedical fields. He joined the “Shanghai Sailing Program” in 2017.
Silk protein fibers produced by silkworms and spiders are renowned for their unparalleled mechanical strength and extensibility arising from their high-β-sheet crystal contents as natural materials. Recently, exciting opportunities for silks in photonics, implantable bioelectronics and nanostructured scaffolds have been reported, revealing the need for innovative approaches to multi-scale fabrication with precision and manufacturing scalability. Silk was reported to be used either as a positive or negative EBL resist through interactions with electron beams given its polymorphic crystalline structure. The water-soluble film can be rendered insoluble by inducing crystallization (that is, beta sheet formation) of the silk protein. The inelastic collision of electrons with crystalline silk results in the formation of short polypeptides which are water-soluble. While in negative EBL using silk proteins where water radiolysis dominates, high electron beam doses are usually needed to form the intermolecular crosslinks to make the proteins water-insoluble. Either amorphous or crystalline silk can be used in both positive and negative tones by tuning the applied electron dosage. Furthermore, we report here for the first time, for crystalline silk exposed to the electron beam, scission of the crosslinked β-sheets tends to occur from top to bottom, resulting in the removal of materials after a water-based development, which is referred to as electron-nanosculpturing (subtractive manufacturing). In contrast, for the amorphous silk exposed to the electron beam, crosslinking of unordered random coils (either intrinsic or deformed from crystalline proteins upon electron irradiations) proceeds from bottom to top, which is referred to as electron-nanosintering (additive manufacturing). Spider silk protein synthesized through genetic engineering with well-defined molecular structure (i.e., average molecular weight and molecular weight distribution) shows better performances (e.g., resolution, contrast and mechanical property) than silk fibroin extracted from natural silk cocoons. These new findings offer new rules to design protein-based architectures of unprecedented resolution and flexibility.