Cancer
metastasis and recurrence are closely associated with immunosuppression
and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and
photothermodynamic therapy (PTT) have been shown to induce immunogenic
cell death (ICD), effectively inhibiting cancer metastasis and recurrence
when combined with immune adjuvants. However, the limited efficacy
of Fenton’s reaction and suboptimal photothermal effect present
significant challenges for successfully inducing ICD through CDT and
PTT. This paper described the synthesis and immunoantitumor activity
of the novel iron–copper-doped folic acid carbon dots (CFCFB).
Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized
via a hydrothermal method, using folic acid and copper gluconate as
precursors. Subsequently, the nanoparticles CFCFB were obtained through
cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic
acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of
carbon dots in CFCFB enhanced the activity of the Fenton reaction,
thereby promoting CDT-induced ICD and increasing the intracellular
oxygen concentration. Additionally, 3BP inhibited cellular respiration,
further amplifying the oxygen concentration. The photothermal conversion
efficiency of CFCFB reached 55.8%, which significantly enhanced its
antitumor efficacy through photothermal therapy. Immunofluorescence
assay revealed that treatment with CFCFB led to an increased expression
of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular
release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover,
the observed downregulation of ARG1 expression indicates a transition
in the tumor microenvironment from an immunosuppressive state to an
antitumor state following treatment with CFCFB. The upregulation of
IL-2 and CD8 expression facilitated the differentiation of effector
T cells, resulting in an augmented population of CD8+ T
cells, thereby indicating the activation of systemic immune response.