pH-Responsive Self-Assembled Upconversion Photosensitizer and RSL3 Synergistically Induce Tumor Ferroptosis

The activatable upconversion photosensitizer is a type of photosensitizer that can be activated in the tumor microenvironment (TEM) to achieve precise photodynamic therapy. As an inducer of ferroptosis, it is difficult for RSL3 to target tumor cells accurately and may be toxic to normal tissues. Thus, we developed a pH-responsive self-assembled near-infrared upconversion photosensitizer (Re-NPs) and encapsulated RSL3 drugs (RSL3@Re-NPs) to induce ferroptosis synergistically. The RSL3@Re-NPs can effectively release RSL3 under acidic conditions in TEM, and they can generate singlet oxygen under 808 nm. Through the combination of RSL3 and a photosensitizer, the specific release of the drug and the accumulation of lipid peroxide were realized. In vitro and in vivo results showed that RSL3@Re-NPs had good biocompatibility and significantly inhibited tumor cell proliferation by inducing cell ferroptosis. This combination strategy provides new ideas and methods for tumor treatment, which is expected to improve the efficacy of tumor treatment and reduce side effects.