Aggregation-Induced Emission Active Copolymers Designed for Stabilizing Cubic Phase Lipid Nanoparticles That Can Be Used for Bioimaging.

Abstract

Fluorescence imaging has become a powerful technique in biomedical engineering and biomaterials science. Fluorescence probes exhibiting aggregation-induced emission (AIE) characteristics stand out as exceptional candidates for imaging due to their photostabilities and sensitivities. However, the hydrophobicity of the AIE functional groups limits their broad applicability. To overcome this limitation, we employed AIE by incorporating tetraphenylethylene (TPE) groups into amphiphilic blocks and random copolymers with varying lengths of 2-(dimethylamino)ethyl methacrylate (DMAEMA) segments. These new polymers demonstrate self-assembly behaviors forming fluorescent, core-shell micelles in aqueous environments and can serve as dual-functional stabilizers for monoolein-based lipid nanoparticles (MO-based LNPs) containing intricate inverse cubic (Q2) and hexagonal (H2) mesophases. Through rational design of incorporating DMAEMA, a pH-dependent enhancement in TPE fluorescent intensity for both nanosystems, the self-assembled polymer micelles and polymer-stabilized LNPs, was achieved. Successful fluorescence imaging of the novel polymer-stabilized LNPs was demonstrated in HeLa cells by confocal microscopy. This study represents the first instance of utilizing TPE- and DMAEMA-based block copolymers as fluorescent stabilizers for LNPs, with tunable fluorescent intensities by variations of DMAEMA block length and environmental pH. These findings underscore the significance of AIE block copolymers with tunable physicochemical properties for fluorescence imaging of nanomaterials in biological systems.