Cerenkov Radiation Induced Photodynamic Therapy Using Chlorin e6-Loaded Hollow Mesoporous Silica Nanoparticles

Abstract

Traditional photodynamic therapy (PDT) requires external light to activate photosensitizers for therapeutic purposes. However, the limited tissue penetration of light is still a major challenge for this method. To overcome this limitation, we report an optimized system that uses Cerenkov radiation for PDT by using radionuclides to activate a well-known photosensitizer (Chlorin e6, Ce6). By taking advantage of hollow mesoporous silica nanoparticles (HMSNs) that can intrinsically radiolabel oxophilic zirconium-89 (89Zr, t1/2 = 78.4 h) radionuclide, as well as possess great drug loading capacity, Ce6 can be activated by Cerenkov radiation from 89Zr in the same nanoconstruct. In vitro cells viability experiments demonstrated dose-dependent cell deconstructions as a function of concentration of Ce6 and 89Zr. In vivo studies show inhibition of tumor growth when mice were subcutaneously injected with [89Zr]HMSN-Ce6 and histological analysis of tumor section showed damage to tumor tissues, implying that reactive oxygen species mediated the destruction. This study offers a way to use internal radiation source to achieve deep-seated tumor therapy without using any external light source for future applications.

Nanoparticles to mediate X‐ray‐induced photodynamic therapy and Cherenkov radiation photodynamic therapy

“…(e) Co‐localization in vivo therapy results. (Reprinted with permission from Shaffer et al (), Kamkaew et al () and Kotagiri et al (). Copyright 2017, 2016 and 2018 American Chemical Society and Nature Publishing Group)…”

“…Later, Thorek, Ogirala, Beattie, and Grimm (2013) studied Cherenkov radiation interacting with quantum dots for secondary Cherenkov-induced fluorescence imaging. Since that time several studies have reported that Cherenkov radiation can be exploited to activate PDT (Hartl, Hirschberg, Marcu, & Cherry, 2016;Kamkaew et al, 2016;Kotagiri, Sudlow, Akers, & Achilefu, 2015). Using Cherenkov radiation to induce PDT offers several potential advantages.…”

Utilizing the power of Cerenkov light with nanotechnology

“…The nanoparticles, termed nanophotosensitizers, were targeted to tumours via transferrin attached to the surface, and the PDT from the combination of titanium dioxide and [ 18 F]-FDG showed a significant survival benefit compared with either of the agents alone. This work utilized the internal CL to photoactivate the nanoconstruct for oxidation-based therapy, for the first time liberating photodynamic therapy from the need of an external excitation source, similar to the internal excitation of fluorochromes 57 , with similar work using 89 Zr-nanoconstruct combinations also demonstrating therapeutic efficacy 58 . This approach is attractive due to the potential utilization of photodynamic therapeutics with clinical radiotracers already in routine use.…”

Design of Cerenkov Radiation–Assisted Photoactivation of TiO2 Nanoparticles and Reactive Oxygen Species Generation for Cancer Treatment

“…Recently, CR was also used as a light source for chemical and therapeutic applications (14)(15)(16). In 2015, Kotagiri et al (15) demonstrated the use of CR generated by the 18 F-FDG radionuclide to activate TiO 2 nanoparticles in vivo to produce reactive oxygen species (ROS) and suppress the growth of cancer cells.…”

“…It has a band gap of 3.2 eV and absorbs UV light efficiently-properties that match the high-intensity regimen of CR. Kamkaew et al (16) reported a system with a 89 Zr radionuclide (Cerenkov radiation source) and chlorin e6 (photocatalyst) and demonstrated its advantage in ROS generation through CR. Two radionuclides-68 Ga and 18 F-were recently studied for their cellular uptake and effectiveness in cancer treatment (23,24).…”