Near-infrared light-activated red-emitting upconverting nanoplatform for T₁-weighted magnetic resonance imaging and photodynamic therapy

Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF₄: 40% Yb, 2% Er@CaF₂ upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn²⁺, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg–Gly–Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T₁-weighted magnetic resonance imaging (T₁-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T₁-weighted MRI diagnosis and PDT of glioma for antitumor therapy. Statement of Significance: A near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (R/G) ratio of NaScF₄: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF₂ shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF₄: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated red-emitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T₁-weighted magnetic resonance imaging agent for tumor diagnosis.