This talk highlights the second generation of nanoscaled amphiphilic macromolecules. These water-soluble polymers are comprised of a highly branched, hydrophobic interior (core) and hydrophilic exterior (shell) to maintain physical properties characteristic of conventional micelles. The variation of alkyl chain length controls the solution and hemolytic stability as well as drug loading capacity and release rate, whereas the carboxylate or amine functional groups of the PEG chain ends are utilized to conjugate targeting molecules. Carboxylic acid groups on the polymer chain ends preferentially and distinctly interact with low-density lipoproteins (LDL) to prevent prolonged retention and aggregation of LDL. In addition to applications in drug delivery, the chain end-functionalized polymers, particularly the carboxylic acid terminal groups, show promise in promoting interactions with biological entities, such as LDL receptor-mediated uptake.