Nanogel Star Polymer Architectures: A Nanoparticle Platform for Modular Programmable Macromolecular Self-Assembly, Intercellular Transport, and Dual-Mode Cargo Delivery

There is a growing demand for the simultaneous, site-localized delivery and expression of tandem functionality within the human body. [1–7] The benefits of dual delivery of functional cargos such as two (synergistic) therapeutics, [8,9] a therapeutic and an imaging agent, [4,10] or dual-mode imaging agents [11,12] have all been recently reported. For many medical applications requiring such in vivo expression of exogenous functional materials, the use of polymeric nanoparticle delivery vehicles of increasingly complex design is envisioned. Currently, organic nanoparticle platforms under development for these purposes include liposomes, [13] dendrimers,[14] and micelles. [15] Alternatively, star polymers (unimolecular, globular, polymer architectures) are an increasingly attractive class of organic nanoparticles for biomedical research purposes. [16–18] Although topographically similar to dendrimers (i.e., a high local density of polymeric arms, surface functionality, and interstitial regions), they lack the synthetic and structural limitations of dendrimers [19,20] and the dynamic instability of micelles [21] and liposomes. [22] Nanogel star polymers, i.e., those with polymer “arms” emanating from a cross-linked polymer core, [23,24] in particular, offer a potential for variation in nanoparticle structure and surface functional, i.e., arm density but are among the most synthetically demanding of polymeric nanostructures to develop. [25–29]