Emodin-Based Nanoarchitectonics with Giant Two-Photon Absorption for Enhanced Photodynamic Therapy

Two-photon-excited photodynamic therapy (TPE-PDT) has significant advantages over conventional photodynamic therapy (PDT). However, obtaining easily accessible TPE photosensitizers (PSs) with high efficiency remains a challenge. Herein, we demonstrate that emodin (Emo), a natural anthraquinone (NA) derivative, is a promising TPE PS with a large two-photon absorption cross-section (TPAC: 380.9 GM) and high singlet oxygen (¹ O₂ ) quantum yield (31.9 %). When co-assembled with human serum albumin (HSA), the formed Emo/HSA nanoparticles (E/H NPs) possess a giant TPAC (4.02×10⁷  GM) and desirable ¹ O₂ generation capability, thus showing outstanding TPE-PDT properties against cancer cells. In vivo experiments reveal that E/H NPs exhibit improved retention time in tumors and can ablate tumors at an ultra-low dosage (0.2 mg/kg) under an 800 nm femtosecond pulsed laser irradiation. This work is beneficial for the use of natural extracts NAs for high-efficiency TPE-PDT.