Nanoparticles derived from amphiphilic hybrid block copolymers (HBCs) have been recognized as promising candidates for a range of applications, including bioimaging, therapeutic delivery, and diagnostics. Comprised of chemically distinct blocks with differing architectures, these unique polymer frameworks exhibit properties that surpass those of conventional amphiphilic polymers. However, a lack of synthetic feasibility has hindered the widespread adoption of amphiphilic HBCs due to challenges posed by the distinct solubility of the blocks, the steric effects of the branched block on copolymerization and purification of end products, and the difficulty of preparing amphiphilic HBCs.Herein, we report the use of aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization to form amphiphilic HBCs and assess their potential as biomaterials for theranostic applications. Comprised of chemically distinct blocks with differing architectures (i.e., dendritic and grafted/linear), these unique polymer frameworks were strategically designed to self-assemble into nanoparticles ideal for simultaneous bioimaging and therapy. The synthesis, physicochemical characterization, and in vitro cell viability of a library of dendritic HBCs and their resulting nanoparticles are discussed. Microscopy (TEM) and dynamic light scattering (DLS)analyses support the formation of aqueous dispersions, yielding polymeric nanoparticles with sizes < 120 nm. The resulting polymer hybrids and their nanoparticles exhibited minimal cell toxicity and dual imaging and therapeutic potential. Results indicate that these polymers and their nanoparticles exhibit properties surpassing those of conventional amphiphilic polymers. This study exemplifies the effect of polymer topology on nanomaterial properties and expands the design space of RAFT polymerization in biomedical research.