Hydrophilic homopolymers of N,N-dimethylacrylamide (DMA) and N-(2-hydroxypropyl) methacrylamide (HPMA), as well as select examples of statistical copolymers with N-acryloxysuccinimide (NAS) were prepared with well-defined molecular characteristics employing a series of new RAFT chain transfer agents containing 1-4 hydrophobic functional groups in the R fragment based on pyren-e, cholesterol, or octadecane, resulting in hydrophilic homopolymers containing between only 6-23 wt % hydrophobic end groups. PolyDMA (PDMA) and polyHPMA (PHPMA) homopolymers, of varying molar masses, with either bis pyrenyl or cholesteryl end groups self-assembled in aqueous media forming spherical vesicles with sizes in the range of several hundred nm up to ca. one micrometer. Lower molar mass PDMA-NAS copolymers with two cholesteryl end-groups at the omega-termini assemble to give clear tubular vesicles, whereas such copolymers of a higher molar mass preferentially form spherical polymersomes. The presence of two spatially close rigid rings at the omega-terminus is shown to be crucial in vesicle formation since a PDMA homopolymer with two octadecyl omega-end-groups self-assembles to yield polymeric micelles with an average hydrodynamic diameter of similar to 20 nm as determined by dynamic light scattering. The presence of a C16 alkyl spacer in the R fragment in a novel dithioester CTA with two pyrenyl functional groups and its use in the polymerization of a PDMA homopolymer yields spherical polymersomes in water, in a similar manner to those formed using a CTA without a spacer, except there is no direct FE-SEM evidence of open-mouth species perhaps indicating that the added flexibility associated with the spacer groups helps facilitate full vesicle closure. The synthesis of a biodegradable bis-pyrenyl dithioester, containing disulfide bridges, facilitates the preparation of PDMA-based polymersomes capable of dithiothreitol-induced pyrene release as evidenced by fluorescence emission spectroscopy. The same biodegradable polymersomes are also shown to be able to sequester the hydrophilic model drug Rhodamine B whose controlled release is demonstrated to be dependent on the presence, or absence, of dithiothreitol as determined by UV-vis spectroscopy.