Theranostic Verteporfin-Conjugated Upconversion Nanoparticles for Cancer Treatment

Photodynamic therapy (PDT) is a highly selective, clinically approved, minimally invasive technique that effectively eliminates cancer cells. Its effectiveness is limited by poor light penetration into tissue and the hydrophobic nature of photosensitizers, highlighting the need for new approaches to treatment. Here, a theranostic upconversion nanoplatform, consisting of a NaYF₄:Yb,Er,Tm,Fe core and a NaHoF₄ shell codoped with Yb, Nd, Gd and Tb ions, was designed to enhance PDT outcomes by integrating multi-wavelength upconversion luminescence, <i>T</i>₂-weighted magnetic resonance imaging (MRI) and PDT. The synthesized core-shell upconversion nanoparticles (CS-UCNPs) were coated with new verteporfin (VP)-conjugated alendronate-terminated poly(<i>N</i>,<i>N</i>-dimethylacrylamide-<i>co</i>-2-aminoethyl acrylate) [Ale-P(DMA-AEA)] grafted with poly(ethylene glycol) (PEG). Under 980 nm NIR irradiation, CS-UCNP@Ale-P(DMA-AEA)-PEG-VP nanoparticles generated reactive oxygen species (ROS) due to the efficient energy transfer between CS-UCNPs and VP. In a pilot preclinical study, intratumoral administration of nanoparticle conjugates to mice, followed by exposure to NIR light, induced necrosis of pancreatic tumor and suppressed its growth.