Glyco-Cloaking Unlocks Cationic Aggregation-Induced Emission Luminogens for Myogenesis Support and On-Demand Photodynamic Antibacterial Action.

Abstract

Antimicrobial resistance threatens both human health and economic stability, urgently demanding antibiotic-free infection strategies. This global crisis brings to the fore a central challenge in antimicrobial material design lying in reconciling potency with biocompatibility, a dilemma acutely epitomized by cationic amphiphilic materials, despite their longstanding therapeutic significance. To address this, we present a glyco-cloaked charge-masking strategy that converts an intrinsically toxic cationic scaffold into a biocompatible and multifunctional platform. By employing a deep-red aggregation-induced emission-active pyridinium scaffold, systematic glycosylation affords eight derivatives in acetyl-protected and deprotected forms. Glycosylation attenuates cationic charge exposure on nanoaggregates, dramatically reducing mammalian cell internalization, cytotoxicity, and hemolysis, while fully preserving robust photodynamic activity with efficient dual-type reactive oxygen species generation, alongside bacterial-targeting capability. Strikingly, the lead compound Man-PEBT enables precise intracellular bacterial imaging and on-demand photodynamic bacterial elimination <i>in vitro</i> and <i>in vivo</i>, concurrently demonstrating negligible myoblast toxicity and exceptional myogenesis compatibility, which redefines the functional scope of cationic materials. This work unites infection control with tissue support in a single platform and establishes glyco-cloaking as a transformative design strategy to bridge the critical efficacy-biocompatibility divide, offering a step toward a more sustainable bioeconomy and safer biomedicine.