Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death.

Abstract

Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an 'eat me' signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.

• Authors: Wei Li, Jie Yang, Lihua Luo, Mengshi Jiang, Bing Qin, Hang Yin, Chunqi Zhu, Xiaoling Yuan, Junlei Zhang, Zhenyu Luo, Yongzhong Du, Qingpo Li, Yan Lou, Yunqing Qiu, Jian You
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 3349 (07 26 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 31350406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Gold

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Cell Death
• Cell Line, Tumor
• Dendritic Cells (immunology)
• Endoplasmic Reticulum (metabolism)
• Endoplasmic Reticulum Stress
• Gold (chemistry)
• Humans
• Hyperthermia, Induced
• Infrared Rays
• Male
• Mice
• Mice, Inbred BALB C
• Nanospheres (chemistry)
• Neoplasms (immunology, metabolism, therapy)
• Photochemotherapy
• Reactive Oxygen Species (metabolism)