Enzyme-triggered aggregation of upconversion nanoparticles for targeted photodynamic therapy via NIR irradiation

A core-shell-shell nanoplatform responsive to alkaline phosphatase (ALP) was developed for efficient tumor targeting and near-infrared (NIR)-activated photodynamic therapy (PDT). Specifically, UCNP@SiO2-Bodipy@FFYp was synthesized by encapsulating upconversion nanoparticles (UCNPs) within a silica shell, embedding bodipy derivatives as photosensitizers, and covalently attaching a phosphorylated peptide (FFYp). F & ouml;rster resonance energy transfer (FRET) from the UCNP emission at 550 nm to bodipy facilitated reactive oxygen species (ROS) generation upon NIR excitation. In the tumor microenvironment, ALP-triggered dephosphorylation converted UCNP@SiO2-Bodipy@FFYp into the more hydrophobic UCNP@SiO2-Bodipy@FFY, thereby promoting tumor cell uptake and tumor-specific accumulation. By leveraging this ALP-responsive targeting strategy alongside the deep-tissue penetration of NIR light, significant tumor growth inhibition was achieved both in vitro and in vivo. Notably, after 15 days of treatment in Balb/c mice bearing HeLa tumors, the tumor volume was reduced by over 95%. Taken together, these results highlight the promise of UCNP@SiO2-Bodipy@FFYp as a tumor-responsive nanoplatform for highly effective, targeted PDT in cancer therapy.