Polypept(o)ide Based Biodegradable Cylindrical Polymer Brushes: Controlling Size, Shape, Surface Functionality, and Stability

High Resolution Image Download MS PowerPoint Slide Cylindrical polymer brushes (CPBs) enable remarkable control over nanoparticle properties solely through sequential polymerization. The spatial dimensions and functionality of the resulting polymeric nanoparticles can be adjusted by the ratio of backbone to side chain length and the chemical nature of both parts. In this work, we present a convenient and straightforward synthetic pathway to polypept(o)ide-based CPBs using a “grafting-from” strategy utilizing poly- l -lysine (pLys) as the macroinitiator backbone and polysarcosine (pSar) as the side chain. End-capping of pSar chains with azido-butyric acid pentafluorophenyl ester enables facile surface functionalization by click chemistry (e.g., dye labeling). This strategy allows for straightforward control over nanoparticle size ( R h from 12 to 41 nm), shape (aspect ratio from 1.7 to 8.3), and molecular weights (from 350 to 2980 kg mol –1 ). Despite the high grafting density of pSar side chains from the pLys backbone (>85%), enzymatic degradation is feasible by the natural protease B from Streptomyces griseus and enables the analysis of pSar side chains upon cleavage ( Đ = 1.03–1.04). Interestingly, these CPBs exhibit thermal stability in phosphate-buffered saline at elevated temperatures (60 °C for 24 h) and display notable circulation in zebrafish embryos (up to 3 days). Therefore, CPBs based on polypept(o)ides not only allow for precise tuning of size, shape, and surface functionality but also display high biocompatibility and extended circulation time in zebrafish, leveraging the stealth-like properties of pSar.