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.