The synthesis and anti-cancer efficacy of endoperoxide modified copper sulfide-ferritin nanocages as PDT and PTT agents

Photodynamic therapy (PDT) using endoperoxides is to produce toxic singlet oxygen of reactive oxygen species through heat from the endoperoxides present in the medium. Compared with conventional PDT, PDT using endoperoxides has some advantages, for instance, in the presence of endoperoxide, singlet oxygen efficiency is not affected by hypoxic environment, because endoperoxides are the source of singlet oxygen. On the other hand, the kinetic stabilities of endoperoxides are important in the body temperature. Another advantage of endoperoxides is that they can produce singlet oxygen upon warming, so regardless of the wavelength of the emitted light, they can selectively produce singlet oxygen in the heated region. The aim of this study is to synthesize core-shell nanocages ( 10-Aft-CuS ) with the synergistic effect of both photothermal therapy (PTT) and PDT by functionalizing the surface of the Apoferritin ( Aft ) nanocage platform with an endoperoxide derivative and forming ultra-small CuS nanoparticles in its inner cavity for the first time. So, first of all, Aft-CuS nanoparticles were obtained by the synthesis of ultra-small CuS nanoparticles in the inner cavity of Aft nanocages. Then, the surfaces of these nanocages have been functionalized with the Compound 10 , an endoperoxide anthracene derivative. While the synthesized nanoparticles in this way have the synergistic effects of PTT and PDT therapies, achieving this with a natural nanoparticle has also been tested in cell cultures in vitro and in mice with progressed melanoma in vivo by increasing the effectiveness against cancer cells. 10-Aft-CuS nanocages showed high anti-tumor efficacy against malignant melanoma in vitro and in vivo. Graphical abstract