Purpurin/Indocyanine Green Nanocomposite for Restricting Glutaminolysis to Enhance Dual Phototherapy of Cancer.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are promising noninvasive cancer treatments owing to their precision and convenience. Indocyanine green (ICG), a dual-functional agent capable of generating both PDT and PTT effects under single-wavelength laser irradiation, is widely explored in oncology. However, ICG faces limitations such as poor bioavailability, rapid systemic clearance, and tumor microenvironment glutathione (GSH) overexpression, which scavenges reactive oxygen species (ROS) and diminishes therapeutic efficacy. To address this, we developed albumin-based nanoparticles (ICG&purpurin@BSA) co-encapsulating ICG and purpurin. Purpurin inhibits mitochondrial glutaminolysis, a metabolic pathway critical for GSH synthesis, thereby reducing GSH-mediated ROS depletion. Flow cytometry and Western blot analyses confirmed significant GSH downregulation. The nanocomposite demonstrated robust anticancer effects in vitro and in vivo, achieving near 90% tumor growth suppression within 12 days. The outcomes of this research demonstrate the benefits of combining biocompatible nanocomposites with glutamine pathway inhibitors and dual phototherapy agent ICG.