Chaperone/Polymer Complexation of Protein-Based Fluorescent Nanoclusters against Silica Encapsulation-Induced Physicochemical Stresses

Silica encapsulation under ambient conditions is commonly used to shield protein-based nanosystems from chemical stress. However, encapsulation-induced photo- and structural instabilities at elevated temperatures have been overlooked. Using bovine serum albumin-capped fluorescent gold nanoclusters (BSA-AuNCs) as a model, we demonstrated that chaperone/polymer layer-by-layer complexation can stabilize the template to resist encapsulation-induced fragmentation/reorganization and emission increases at 37 °C or higher temperatures. We first wrapped BSA-AuNCs with α-crystallin chaperones (α-Crys) to gain the highest thermal stability at a 1:50 molar ratio and then enfolded BSA-AuNC/α-Crys with thermoresponsive poly-