Nanosized core–shell bio-hybrid microgels and their internal structure

Microgels are versatile materials with applications across biomedicine, materials science, and beyond. Their controllable size and composition enables tailoring specific properties, yet characterizing their internal structures on the nanoscale remains challenging. Super-resolution fluorescence microscopy (SRFM) effectively analyzes sub-μm structures, including microgels, offering a tool for investigating more complex systems such as core-shell microgels. Understanding their internal structure, in particular interpenetration at the soft-soft interface between core and shell and accessibility for guest molecules, is vital for rationally designing predictable functionalities. This study examines the core-shell morphology and the accessibility for guest molecules of bio-hybrid DNA-poly(<i>N</i>-isopropylmethacrylamide) microgels at three stages of shell polymerization using SRFM. Covalent fluorescence labeling probes the core polymer, co-polymerized with <i>N</i>,<i>N</i>'-bis(acryloyl)cystamine, which provides visual insight into core and shell compartmentalization. The results demonstrate core polymer interpenetration into the shell without compromising its original structure, and additionally allow us to determine the size- and hydrophobicity dependent accessibility of the microgel core. This, offering new perspectives on the internal architecture of core-shell microgels, contributes to the in-depth understanding of their complex behavior, potentially guiding the rational design of new microgel drug delivery systems, taking into account the complex interplay of polarity, size and charge of guest molecules.