In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers

A limitation of photodynamic therapy (PDT) is the depth of penetration of visible light needed for activation of the photosensitizers, restricting treatment to tumors on or just under the skin’s surface or those lining internal organs and cavities. Niagara Muhammad Idris and colleagues have addressed this issue by developing upconversion fluorescent nanoparticles (UNCs) that convert deeper penetrating near-infrared light to visible wavelengths without sacrificing efficacy for singlet oxygen (1O2) production. The group tested the UNCs in vivo in a subcutaneous mouse tumor model using a dual-sensitizer approach for greater PDT efficacy. Conventional photodynamic therapy (PDT) is limited by the penetration depth of visible light needed for its activation. Here we used mesoporous-silica–coated upconversion fluorescent nanoparticles (UCNs) as a nanotransducer to convert deeply penetrating near-infrared light to visible wavelengths and a carrier of photosensitizers. We also used the multicolor-emission capability of the UCNs at a single excitation wavelength for simultaneous activation of two photosensitizers for enhanced PDT. We showed a greater PDT efficacy with the dual-photosensitizer approach compared to approaches using a single photosensitizer, as determined by enhanced generation of singlet oxygen and reduced cell viability. In vivo studies also showed tumor growth inhibition in PDT-treated mice by direct injection of UCNs into melanoma tumors or intravenous injection of UCNs conjugated with a tumor-targeting agent into tumor-bearing mice. As the first demonstration, to the best of our knowledge, of the photosensitizer-loaded UCN as an in vivo –targeted PDT agent, this finding may serve as a platform for future noninvasive deep-cancer therapy.