Endoplasmic Reticulum Targeting to Amplify Immunogenic Cell Death for Cancer Immunotherapy.
Nano Lett
; 20(3): 1928-1933, 2020 03 11.
Article
em En
| MEDLINE
| ID: mdl-32073871
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',4â³,4'â³-(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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
/
Retículo Endoplasmático
/
Estresse do Retículo Endoplasmático
/
Imunoterapia
/
Raios Infravermelhos
/
Neoplasias Experimentais
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article