PDT
PDT
has been studied as an immunogenic cell death (ICD) inducer for
eliciting direct tumor-killing effects through the creation of tumor
antigen pools with danger signals that promote cancer-specific
immunity[20]. Photosensitizers (PS) can produce reactive oxygen
species (ROS) in response to exposure to a certain wavelength, which can
then kill surrounding cancer cells by necrotic or apoptotic cell
death[20]. Owing to the highly enriched distinctive physical and
chemical characteristics, CDs have been applied in the synergistic
treatment of PDT and immunotherapy [21]. Kimet
al. designed chlorin e6 (Ce6)-loaded pH-sensitive CDs (Ce6@IDCDs) to
establish superior antitumor immunity[23]. At tumoral pH 6.5, Ce6
was released four times compared with the release at physiological pH
7.4. In the bilateral CT-26-bearing mice model, the Ce6@IDCDs elicited
significant anti-tumor effects at laser-treated-primary tumor regions
via ROS generation. Moreover, Ce6@IDCDs upon laser irradiation recruited
a large amount of activated CD8+ T cells, NK cells,
and mature DCs into tumor tissue and inhibited tumor growth even at
untreated sites[23]. The immune checkpoint inhibitors in particular
programmed death ligand 1 (PD-L1) and its receptor PD-1 have been able
to reactivate dysfunctional and worn-out T cells, producing retention
effects in 50-80% of tumor patients[3, 9, 24]. To this end, Zhanget al. developed the nanoparticle γ-PGA@GOx@Mn,Cu-CDs, which
showed a long retention time at the tumor microenvironment and could
further target cancer cells[25]. It displayed both photothermal and
photodynamic effects under laser irradiation at 730 nm. By
synergistically combining check-point-blockade therapy, this
nanoparticle could activate systematic anti-tumor immune response which
ablated primary and distant tumors[25] (Figure 1a). Overall,
synergistic PDT and immunotherapy will be the main development direction
of CDs in the removal of tumors, the inhibition of distant cancers, and
the prevention of tumor relapse.