Optimized Two-Photon
Imaging by Stimuli-Responsive
Peptide Self-Assembly Facilitates Self-Assisted Counteraction of Cisplatin-Resistance
in Cancer Cells
Accurate diagnosis and effective treatment of tumors
remain significant
clinical challenges. While fluorescence imaging is essential for tumor
detection, it has limitations in terms of specificity, penetration
depth, and emission wavelength. Here, we report a novel glutathione
(GSH)-responsive peptide self-assembly excimer probe (pSE) that optimizes two-photon tumor imaging and self-assisted counteraction
of the cisplatin resistance in cancer cells. The GSH-responsive self-assembly
of pSE induces a monomer–excimer transition of
coumarin, promoting a near-infrared redshift of fluorescence emission
under two-photon excitation. This process enhances penetration depth
and minimizes interference from biological autofluorescence. Moreover,
the intracellular self-assembly of pSE impacts GSH homeostasis,
modulates relevant signaling pathways, and significantly reduces GSTP1
expression, resulting in decreased cisplatin efflux in cisplatin-resistant
cancer cells. The proposed self-assembled excimer probe not only distinguishes
cancer cells from normal cells but also enhances the efficacy of cisplatin
chemotherapy, offering significant potential in tumor diagnosis and
overcoming cisplatin–resistant tumors.