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

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 an oxophilic zirconium-89 (⁸⁹Zr, t_1/2 = 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 cell viability experiments demonstrated dose-dependent cell deconstruction as a function of the 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 the tumor section showed damage to tumor tissues, implying that reactive oxygen species mediated the destruction. This study offers a way to use an internal radiation source to achieve deep-seated tumor therapy without using any external light source for future applications.