Utilizing dual-pathway energy transfer in upconversion nanoconjugates for reinforced photodynamic therapy

Enhancing the therapeutic effect of existing treatments or developing new non-invasive treatments are important measures to achieve high-efficiency treatment of malignant tumors. Photodynamic therapy (PDT) is an emerging treatment modality, and the key for achieving high-efficiency PDT is to select light with strong tissue penetration depth and enhance the generation of reactive oxygen species (ROS). Although the upconversion nanoparticles (UCNPs) modified with the photosensitizers could achieve PDT with strong penetration depth under near-infrared light irradiation, the ROS generated by traditional single-pathway PDT is still insufficient. Herein, we developed a novel nanoconjugate (UCNP-Ce6/AIEgen) for dual-pathway reinforced PDT, in which the UCNPs were co-modified with chlorin e6 (Ce6) and luminogen with aggregation-induced emission (AIEgen). Due to the presence of AIEgen, UCNP-Ce6/AIEgen could avoid aggregation-caused luminescence quenching in biological water environments and convert upconversion luminescence (UCL) of UCNPs to Ce6-activatable fluorescence. Therefore, under the irradiation of 808 nm laser, UCNP-Ce6/AIEgen can not only undergo direct lanthanide-triplet energy transfer to activate Ce6, but also convert the UCL of UCNPs to the light that can activate Ce6 through Fӧrster resonance energy transfer to generate more ROS, thus promoting tumor cell apoptosis. This work broadens the applications of nanoconjugates of lanthanide-based inorganic materials and organic dyes, and provides a conception for reinforced PDT of tumors.