| In this thesis work, I designed and synthesized a series of small molecules that form supramolecular assemblies to selectively target cancer cells or control the cell fates, which have potential applications in biology and medicine. There are eight chapters in the dissertation. Chapter 1 gives a detailed review on self-assembly and enzyme-instructed self-assembly of small molecules to target cancer cells or control the cell fates over the past decade. Chapter 2 reports that ALP-generated D-tripeptidic nanofibrils promiscuously activate extrinsic cell death signaling for selectively killing cancer cells, likely by presenting the autocrine death ligands (e.g., TNF?, or TRAIL) to their cognate receptors (e.g., TNFR1/2, DR3, DR4, and DR5) in juxtacrine manner, as well as directly clustering the receptors (e.g., CD95). Chapter 3 shows that an underexplored generic difference---overexpression of ectophosphatases---between cancer and normal cells triggers the D-tyrosine phosphate decorated magnetic nanoparticles to adhere selectively on cancer cells upon catalytic dephosphorylation, which enables magnetically separation of cancer cells from mixed population of cells (e.g., co-cultured cancer cell and stromal cells). Chapter 4, for the first time, demonstrates the use of enzymatic reaction from ectoenzymes (e.g., ALPP) to actively modulate the surface composition of magnetic nanoparticles for selectively binding to cancer cells without involving specific ligand-receptor interactions or the use of antibodies. Chapter 5 shows the use of chirality to control the reaction-diffusion process of nanoparticles for selectively inhibiting cancer cells. L-phosphotyrosine decorated NPs are innocuous to cells, but D-phosphotyrosine decorated ones selectively inhibit cancer cells. Chapter 6 reports the use of molecular self-assembly to sidestep the laborious synthesis of complex glycans for promoting the proliferation of murine embryonic stem (mES) cells. Chapter 7 reports the use of enzyme to instruct the self-assembly of the nucleoside of adenosine in water to provide a new class of molecular nanofibers/hydrogels as functional soft materials. Chapter 8 reports the design and characterization of nucleopeptides that self-assemble in water and are able to interact with single stranded DNA (ssDNA), the plasmid DNA and deliver hairpin DNA into cells. |
