Enhanced Immunogenic Cell Death by Apoptosis/Ferroptosis Hybrid Pathway Potentiates PD-L1 Blockade Cancer Immunotherapy
- Authors
- Jeong, Seong Dong; Jung, Bo-Kyeong; Lee, DaeYong; Ha, JongHoon; Chang, Han-Gyu; Lee, Jeongmin; Lee, Susam; Yun, Chae-Ok; Kim, Yeu-Chun
- Issue Date
- Dec-2022
- Publisher
- AMER CHEMICAL SOC
- Keywords
- apoptosis; ferroptosis hybrid pathway; immunogenic cell death; immune checkpoint blockade; combination cancer immunotherapy
- Citation
- ACS BIOMATERIALS SCIENCE & ENGINEERING, v.8, no.12, pp.5188 - 5198
- Indexed
- SCIE
SCOPUS
- Journal Title
- ACS BIOMATERIALS SCIENCE & ENGINEERING
- Volume
- 8
- Number
- 12
- Start Page
- 5188
- End Page
- 5198
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/185178
- DOI
- 10.1021/acsbiomaterials.2c00950
- Abstract
- Even though chemotherapy regimens for treating cancer by inducing apoptosis are extensively utilized, their therapeutic effect is hindered by multiple limitations. Thus, a combination of other types of anticancer modalities is urgently needed. Herein, a 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) for apoptosis/ferroptosis-mediated immunogenic cell death (ICD) is reported. By coating TA-Fe3+ on the surface of DOX-loaded micelles, an apoptotic agent and a ferroptotic agent are simultaneously delivered into the cancer cells and induce cell death. Furthermore, the intracellular oxidative environment generated by the apoptosis/ferroptosis hybrid pathway stimulates the endoplasmic reticulum (ER) and leads to ICD induction. The in vivo results show that the combination treatment of TFDD and anti-programmed death-ligand 1 antibodies (anti-PD-L1) considerably inhibits tumor growth and improves antitumor immunity by activating CD4+ and CD8+ T cells and decreasing the ratio of regulatory T cells (Treg) to CD4+ T cells. This study suggests that the apoptosis/ferroptosis-mediated ICD inducer may offer a potent strategy for enhanced cancer immunotherapy.
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