The Enhanced Permeability and Retention (EPR) effect has seen considerable exploration by many researchers since it’s discovery by Maeda et al in 1985. Polymers and nanoparticles with a long blood residence half-life can accumulate in some tumour tissues, allowing for the delivery of either diagnostic or therapeutic payloads. We have contributed to this field by the development of methodology to prepare radiolabeled dendrimers which are suitable for EPR effect accumulation with a variety of peripheral functionalities. The first of these was a 99mTc-labeled fifth generation dendron which was peripherally functionalized with low molecular weight poly(ethylene glycol) chains, which was observed to accumulate in xenograft mouse tumours over the course of 6 hours. This work led to the development of improved synthetic means for the preparation of high generation dendrimers with complex peripheral functionality, which hinged on the use of the Strain Promoted Alkyne-Azide Cycloaddition reaction to give high generation dendrimers by a convergent approach. This resulted in the facile preparation of dendrimers with challenging peripheral functionality in reaction times as short as 5 minutes. This SPAAC based convergent synthesis approach was used to prepare 99mTc labeled sulfobetaine and carboxybetaine dendrons of the sixth generation, and these compounds were found to have a size greater than the renal clearance threshold of ~ 5 nm, though it was found that labeling with [99mTc(CO)3]+ was not possible without extensive degradation of the zwitterionic dendrimers. Finally, the dendritic architecture explored for imaging was adapted for use in shielding an enzyme from macromolecules while retaining activity against the native small molecule substrate, and we found that conjugation of high-generation bis-MPA dendrons to α-chymotrypsin was an effective way to eliminate enzyme activity against macromolecules while preserving efficacy against small substrates, indicating this approach may be an effective way to shield proteins from the immune system without interfering with their desired function. This work illustrates the ability to radiolabel polyester dendrimers for tumour imaging through the EPR effect. In addition, it has demonstrated that polymer architecture has a large impact on the properties of polymer-protein conjugates and gives evidence of unique properties that are imparted by the conjugation of high-generation dendrimers onto a protein. / Thesis / Doctor of Science (PhD)