Enhanced Immunogenic Cell Death by Apoptosis/Ferroptosis Hybrid Pathway Potentiates PD-L1 Blockade Cancer Immunotherapy

• DOI: 10.1021/acsbiomaterials.2c00950
• Publication Date: 2022-11-30T18:25:55Z
• Authors: Seong Dong Jeong; Bo-Kyeong Jung; DaeYong Lee; JongHoon Ha; Han-Gyu Chang; Jeongmin Lee; Susam Lee; Chae-Ok Yun; Yeu-Chun Kim
• Keywords: Immunogenic cell death; Cancer Immunotherapy

Even though chemotherapy regimens for treating cancer by inducing apoptosis are extensively utilized, their therapeutic effect is hindered multiple limitations. Thus, a combination of other types anticancer modalities urgently needed. Herein, tannic acid (TA)-Fe3+-coated doxorubicin (DOX)-encapsulated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (ammonium salt) (DSPE-PEG) micelle (TFDD) apoptosis/ferroptosis-mediated immunogenic cell death (ICD) reported. By coating TA-Fe3+ on the surface DOX-loaded micelles, an apoptotic agent and ferroptotic simultaneously delivered into cells induce death. Furthermore, intracellular oxidative environment generated apoptosis/ferroptosis hybrid pathway stimulates endoplasmic reticulum (ER) leads to ICD induction. The in vivo results show that treatment TFDD anti-programmed death-ligand 1 antibodies (anti-PD-L1) considerably inhibits tumor growth improves antitumor immunity activating CD4+ CD8+ T decreasing ratio regulatory (Treg) cells. This study suggests inducer may offer potent strategy enhanced immunotherapy.