Europium-Diethylenetriaminepentaacetic Acid Loaded Radioluminescence Liposome Nanoplatform for Effective Radioisotope-Mediated Photodynamic Therapy.

Abstract

Photodynamic therapy (PDT) is an effective anticancer strategy with a higher selectivity and fewer adverse effects than conventional therapies; however, shallow tissue penetration depth of light has hampered the clinical utility of PDT. Recently, reports have indicated that Cerenkov luminescence-induced PDT may overcome the tissue penetration limitation of conventional PDT. However, the effectiveness of this method is controversial because of its low luminescence intensity. Herein, we developed a radiolabeled diethylenetriaminepentaacetic acid chelated Eu³⁺ (Eu-DTPA)/photosensitizer (PS) loaded liposome (Eu/PS-lipo) that utilizes ionizing radiation from radioisotopes for effective <i>in vivo</i> imaging and radioluminescence-induced PDT. We utilized Victoria blue-BO (VBBO) as a PS and observed an efficient luminescence resonance energy transfer between Eu-DTPA and VBBO. Furthermore, ⁶⁴Cu-labeled Eu lipo demonstrated a strong radioluminescence with a 2-fold higher intensity than Cerenkov luminescence from free ⁶⁴Cu. In our radioluminescence liposome, radioluminescence energy transfer showed a 6-fold higher energy transfer efficiency to VBBO than Cerenkov luminescence energy transfer (CLET). ⁶⁴Cu-labeled Eu/VBBO lipo (⁶⁴Cu-Eu/VBBO lipo) showed a substantial tumor uptake of up to 19.3%ID/g by enhanced permeability and retention effects, as revealed by <i>in vivo</i> positron emission tomography. Finally, the PDT using ⁶⁴Cu-Eu/VBBO lipo demonstrated significantly higher <i>in vitro</i> and <i>in vivo</i> therapeutic effects than Cerenkov luminescence-induced PDT using ⁶⁴Cu-VBBO lipo. This study envisions a great opportunity for clinical PDT application by establishing the radioluminescence liposome which has high tumor targeting and efficient energy transfer capability from radioisotopes.