Endoplasmic Reticulum Targeting to Amplify Immunogenic Cell Death for Cancer Immunotherapy

Hongzhang Deng; Zijian Zhou; Weijing Yang; Li-Sen Lin; Sheng Wang; Gang Niu; Jibin Song; Xiaoyuan Chen

doi:10.1021/acs.nanolett.9b05210

Endoplasmic Reticulum Targeting to Amplify Immunogenic Cell Death for Cancer Immunotherapy

Nano Lett. 2020 Mar 11;20(3):1928-1933. doi: 10.1021/acs.nanolett.9b05210. Epub 2020 Feb 21.

Authors

Hongzhang Deng^{1

2}, Zijian Zhou², Weijing Yang², Li-Sen Lin², Sheng Wang², Gang Niu², Jibin Song¹, Xiaoyuan Chen²

Affiliations

¹ MOE key laboratory for analytical science of food safety and biology, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
² Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Bethesda, Maryland 20892 United States.

PMID: 32073871
DOI: 10.1021/acs.nanolett.9b05210

Abstract

Immunogenic cell death (ICD) elicited by photodynamic therapy (PDT) is mediated through generation of reactive oxygen species (ROS) that induce endoplasmic reticulum (ER) stress. However, the half-life of ROS is very short and the intracellular diffusion depth is limited, which impairs ER localization and thus limits ER stress induction. To solve the problem, we synthesized reduction-sensitive Ds-sP NPs (PEG-s-s-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] nanoparticles) loaded with an efficient ER-targeting photosensitizer TCPP-T^ER (4,4',4″,4'″-(porphyrin-5,10,15,20-tetrayl)tetrakis(N-(2-((4-methylphenyl)sulfonamido)ethyl)benzamide). The resulting Ds-sP/TCPP-T^ER NPs could selectively accumulate in the ER and locally generate ROS under near-infrared (NIR) laser irradiation, which induced ER stress, amplified ICD, and activated immune cells, leading to augmented immunotherapy effect. This study presents a novel ICD amplifying, ER-targeting PDT strategy that can effectively eradicate primary tumors under NIR exposure, as well as distant tumors through an abscopal effect.

Keywords: Endoplasmic reticulum (ER) stress; Immunogenic cell death (ICD); Photodynamic therapy; abscopal effect.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Death / drug effects
Cell Death / immunology
Cell Line, Tumor
Drug Delivery Systems*
Endoplasmic Reticulum Stress* / drug effects
Endoplasmic Reticulum Stress* / immunology
Endoplasmic Reticulum Stress* / radiation effects
Endoplasmic Reticulum* / immunology
Endoplasmic Reticulum* / pathology
Immunotherapy*
Infrared Rays*
Mice
Mice, Inbred BALB C
Neoplasms, Experimental* / immunology
Neoplasms, Experimental* / pathology
Neoplasms, Experimental* / therapy
Reactive Oxygen Species / immunology

Substances

Reactive Oxygen Species