Förster resonance energy transfer-based evaluation of biodegradability in silica and organosilica cross-linked...

Cross-linking is an effective strategy to enhance the structural stability of the amphiphilic polymeric micelles. Silica and organosilica precursors can serve as cross-linking agents, forming rigid silica shells that encapsulate the hydrophobic micellar core. Compared to covalently cross-linked micelles, silica cross-linked micelles enjoy several advantages, including facile preparation route, excellent stability, favorable biocompatibility and abundant silanol groups abundant silanol groups for functionalization. However, the limited biodegradability of silica raises significant clinical concerns for intravenously administered drug carriers. In this work, we employed Förster Resonance Energy Transfer (FRET) to evaluate the biodegradability of silica cross-linked micelles in vitro and in vivo. Near-infrared fluorescent dyes Cyanine5 and Cyanine5.5 were conjugated to the silica shell as the FRET pair. As silica degrades, the FRET interaction is decoupled, enabling real-time monitoring of the degradation via changes in fluorescence intensity ratios. Our results reveal that residual silanol groups in the silica shell of the cross-linked micelles contributed to their biodegradability. Furthermore, organosilica cross-linked micelles incorporating disulfide bonds within the silica framework exhibited enhanced degradability in the presence of glutathione, underscoring their potential for stimuli-responsive drug delivery applications.