In Situ Self‐Assembled J‐Aggregate Nanofibers of Glycosylated Aza‐BODIPY for Synergetic Cell Membrane Disruption and Type I Photodynamic Therapy

Abstract

AbstractThe in situ self‐assembly of exogenous molecules is a powerful strategy for manipulating cellular behavior. However, the direct self‐assembly of photochemically inert constituents into supramolecular nano‐photosensitizers (PSs) within cancer cells for precise photodynamic therapy (PDT) remains a challenge. Herein, we developed a glycosylated Aza‐BODIPY compound (LMBP) capable of self‐assembling into J‐aggregate nanofibers in situ for cell membrane destruction and type I PDT. LMBP selectively entered human hepatocellular carcinoma HepG2 cells and subsequently self‐assembled into intracellular J‐aggregate nanovesicles and nanofibers through supramolecular interactions. Detailed studies revealed that these J‐aggregate nanostructures generated superoxide radicals (O2−⋅) exclusively through photoinduced electron transfer, thus enabling effective PDT. Furthermore, the intracellular nanofibers exhibited an aggregation‐induced retention effect, which resulted in selective toxicity to HepG2 cells by disrupting their cellular membranes and synergizing with PDT for powerful tumor suppression efficacy in vivo.