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-TER (4,4',4″,4'″-( porphyrin-5,10,15,20-tetrayl)tetrakis(N-(2-((4-methylphenyl)sulfonamido)ethyl) benzamide). The resulting Ds-sP/ TCPP-TER 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.
|
Authors | Hongzhang Deng, Zijian Zhou, Weijing Yang, Li-Sen Lin, Sheng Wang, Gang Niu, Jibin Song, Xiaoyuan Chen |
Journal | Nano letters
(Nano Lett)
Vol. 20
Issue 3
Pg. 1928-1933
(03 11 2020)
ISSN: 1530-6992 [Electronic] United States |
PMID | 32073871
(Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
|
Topics |
- Animals
- Cell Death
(drug effects, immunology)
- Cell Line, Tumor
- Drug Delivery Systems
- Endoplasmic Reticulum
(immunology, pathology)
- Endoplasmic Reticulum Stress
(drug effects, immunology, radiation effects)
- Immunotherapy
- Infrared Rays
- Mice
- Mice, Inbred BALB C
- Neoplasms, Experimental
(immunology, pathology, therapy)
- Reactive Oxygen Species
(immunology)
|