(438g) pH-Responsive Nano- and Microparticles with Tunable Chirality for Protein Separation

It has long been observed that different stereoisomers of small molecules exhibit dramatically different biological activities, ranging from medicinal to poisonous. In contrast, the influence of larger-scale chirality, such as nano- and mesoscale anisotropy effects on bioactivity and biological interactions, remains largely unexplored. This gap in understanding is due to the challenges of using atomically precise computational methods to predict such interactions within large systems and the difficulty in designing and synthesizing materials with controllable chirality at multiple scales. Despite the absence of complex chiral materials with tunable multi-scale chirality that interact with biomolecules, recent studies have demonstrated enantiomer-dependent immunological responses to nanoparticles with different nanoscale chirality.

Here, we report the repertoire of self-assembled chiral microparticles composed of hierarchically organized nanosheets and linear supramolecular polymers, functionalized with amino acids. These particles, whose size, morphology, and chemical composition can be tuned by adjusting pH and physicochemical conditions, exhibit controllable chirality at multiple scales. We demonstrate that these particles display chirality-dependent affinity to various biomacromolecules, enabling the selective separation of specific proteins from complex biological fluids. For instance, we show that certain types of these spiky particles specifically trap apolipoproteins associated with cardiovascular and neurodegenerative diseases. Due to the synthesis simplicity, scalability, and broad potential for chemical modifications of the chiral structure, this approach holds significant promise for biomedical applications and diagnostics.