Biomacromolecular Gold Nanocomplexes Induce Membrane Rupture and Immunogenic Cell Death

Protein-based biomacromolecules have emerged as versatile building blocks for biomedical materials owing to their structural complexity and biological functionality. Herein, we report the biomacromolecular gold nanocomplexes through the assembly of catalase and engineered gold nanoparticles and investigate their ability to modulate cellular membranes for cancer immunotherapy. Assembly of catalase with gold nanoparticles generated stable biomacromolecular nanocomplexes (AuCAT) with enhanced cellular membrane affinity. By modulating the protein-nanoparticle composition, the interfacial behaviour of the assemblies could be precisely controlled, resulting in distinct membrane interactions. Notably, AuCAT2 exhibited strong membrane-disruptive activity, inducing progressive membrane destabilization and extensive membrane fragmentation. Time-resolved confocal imaging revealed continuous accumulation of membrane-derived debris around treated cells, indicating direct disruption of plasma membrane integrity by the biomacromolecular assemblies. Unlike conventional intracellular therapeutic strategies, AuCAT2 exerts its anticancer activity through physical membrane disruption. This process triggered rapid lytic cell death accompanied by substantial LDH release and promoted the release of intracellular danger-associated molecular signals associated with immunogenic cell death (ICD). Importantly, catalase retained its intrinsic enzymatic function after assembly, demonstrating that biological activity can be preserved while simultaneously introducing new membrane-active properties through nanoassembly. Collectively, this study establishes biomacromolecular assembly as an effective nanoplatform for engineering cell-material interfaces and demonstrates that membrane-active biomacromolecular gold nanocomplexes can serve as a promising therapeutic modality for inducing immunogenic cancer cell death.