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 in vivo 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 in vivo positron emission tomography. Finally, the PDT using 64Cu-Eu/VBBO lipo demonstrated significantly higher in vitro and in vivo 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.

All‐In‐One Biomimetic Nanoplatform Based on Hollow Polydopamine Nanoparticles for Synergistically Enhanced Radiotherapy of Colon Cancer

“…The abnormal vasculature cannot transport sufficient oxygen for rapidly proliferating cancer cells, resulting in RT resistance. [9][10][11] Thus, relieving tumor hypoxia is essential to enhance the efficacy of RT. Recently, many strategies have been provided to overcome hypoxia in tumor tissue, including delivering oxygen directly, boosting blood flow in tumor tissue, and in situ oxygen production.…”

“…Conventional photodynamic therapy (PDT) has shown great effectiveness in tumor treatment and is used clinically, but the major drawback of PDT is the limited light penetration depth. [9][10][11] With the high tissue-penetrability of X-rays, researchers proposed that X-ray induced photodynamic therapy (X-PDT) may overcome the drawback of PDT and improve therapeutic outcomes for deep-seated cancer. The principle of X-PDT is to use an energy transducer to transfer X-rays to optical luminescence and initiate the RT and PDT processes.…”

Multichannel Lanthanide-Doped Nanoprobes Improve Diagnostic Performance

“…After one or more photons are absorbed, electrons at the ground state are excited to a higher energy level, followed by singlet–singlet or triplet-singlet electronic relaxation, which are termed fluorescence and phosphorescence, respectively. Apart from photoluminescence, there are also several typical luminescence modes for constructing nanoprobes, such as radioluminescence and bioluminescence. , Introducing luminescent signals into nanoprobes requires a luminescent transition-metal nucleus, molecular dyes, or quantum dots. As far as we are concerned, regarding radioactive signals, the introduction process requires a radioactive nucleus (e.g., 18 F or 177 Lu).…”

“…Apart from photoluminescence, there are also several typical luminescence modes for constructing nanoprobes, such as radioluminescence and bioluminescence. 33,34 Introducing luminescent signals into nanoprobes requires a luminescent transition-metal nucleus, molecular dyes, or quantum dots. As far as we are concerned, regarding radioactive signals, the introduction process requires a radioactive nucleus (e.g., 18 F or 177 Lu).…”

Bioresorbable Microdroplet Lasers as Injectable Systems for Transient Thermal Sensing and Modulation

“…Recent strategies in remote temperature sensing exploit optically active materials, such as molecular probes, , upconversion nanoparticles, or quantum dots , assembled into nano/microparticles − for direct injection into biological tissues. Careful selection of materials and structures enables excitation at wavelengths of relative tissue transparancy, with consequent radiation of light that can pass back through the tissue for remote detection.…”