Over the past few decades, polymerization-induced self-assembly (PISA) has become a well-known one-step synthetic procedure for the manufacture of surfactant-free high-solids block copolymer nanoparticles. The robustness and versatility of PISA have made it possible to design nano-objects for many applications, such as biomedical applications with potential use in drug delivery. For instance, PISA processes have been developed for the in situ encapsulation of enzymes and proteins into polymer nanoparticles, as well as synthesis of polymer-protein bioconjugate nanoparticles. Physical encapsulation of drugs and their grafting onto polymer nanoparticles post-PISA have also been studied. However, all these systems are based on non-degradable vinyl polymers, which could lead to cumulative toxicity when administered in vivo, thus compromising any potential clinical translation. Although some work has reported aqueous suspensions of degradable nano- objects by PISA, either by copolymerization of vinyl monomers with cyclic ketene acetals (CKA), cyclic allylic sulfides or thionolactones, via radical ring-opening polymerization (rROPISA), or by ring-opening polymerization of N-carboxyanhydrides, all these examples were more fundamental and did not concern drug loading and delivery.