Antibacterial Theranostic Agents with Negligible Living Cell Invasiveness: AIE-Active Cationic Amphiphiles Regulated by Alkyl Chain Engineering

To address the threat of bacterial infection in the following
post-antibiotic
era, developing effective antibacterial approaches is of utmost urgency.
Theranostic medicine integrating diagnosis and therapy is a promising
protocol to fight against pathogenic bacteria. But numerous reported
antibacterial theranostic materials are disclosed to be trapped in
the excessive invasiveness to living mammal cells, leading to false
positives and possible biosafety risks. Herein, a series of cationic
pyridinium-substituted phosphindole oxide derivatives featuring aggregation-induced
emission are designed, and alkyl chain engineering is conducted to
finely tune their hydrophobicity and investigate their bioaffinity
preference for living mammal cells and pathogenic bacteria. Most importantly,
an efficient theranostic agent (PyBu-PIO) is acquired that is free
from living cell invasiveness with negligible cytotoxicity and yet
holds a good affinity for Gram-positive bacteria, including drug-resistant
strains, with a superior inactivating effect. Externally applying
PyBu-PIO onto Gram-positive bacteria-infected skin wounds can achieve
creditable imaging effects and successfully accelerate the healing
processes with reliable biosafety. This work proposes living cell
invasiveness as a criterion for antibacterial theranostic materials
and provides important enlightenment for the design of antibacterial
theranostic materials.