Work

Encoding Biological Selectivity Through Positional Isomerism of Phosphindole Oxide AIEgens for Targeted Photodynamic Therapy

Year: 2026

Type: article

Abstract: Discriminating biological targets via their intrinsic biophysical signatures offers a promising alternative to classical lock-and-key recognition, yet remains constrained by simplistic design. Herein, we present a programmable molecular strategy that leverages configurational isomerism on a phosphindole oxide (PIO) scaffold as a decisive variable for encoding biological selectivity. Strategic substitution at geometrically defined positions generates isomeric pairs with distinct conformational preferences, aqueous self-assembly behaviors, and surface electrostatic landscapes. These isomer-dependent divergences translate into sharply differentiated biological staining patterns. One isomer enables selective labeling of cancer over normal mammalian cells and preferential engagement with bacterial versus mammalian cells, while its counterpart functions as a broad-spectrum staining agent. By integrating with the inherent photodynamic activity of the PIO framework, we achieve effective tumor suppression and accelerated healing of infected wounds in vivo with favorable biosafety. This work establishes positional isomerism as a generalizable design dimension for encoding biophysical selectivity, providing molecular-level guidance for next-generation theranostic and precision medicine platforms.

Source: Advanced Materials

DOI: 10.1002/adma.74291

Authors: Jianqing Li, Zeyan Zhuang, Yiwen Liao, Ping Jiang, Ben Zhong Tang, Zujin Zhao