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.