期刊
BIOMATERIALS
卷 295, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2023.122064
关键词
Self-immolative polymer; Oxidative stress; Endoplasmic reticulum stress; Immunogenic cell death; Cancer immunotherapy
To enhance the immunogenicity of Doxorubicin (DOX), researchers developed a ROS-responsive self-immolative polymer (R-SIP) that efficiently destroys redox homeostasis in cancer cells. The DOX-encapsulated R-SIP (DR-SIP) induces immunogenic cell death and promotes dendritic cell maturation. In vivo studies showed that DR-SIP significantly inhibits tumor growth.
Doxorubicin (DOX), widely used as an anticancer drug, is considered an immunogenic cell death (ICD) inducer that enhances cancer immunotherapy. However, its extended application as an ICD inducer has been limited owing to poor antigenicity and inefficient adjuvanticity. To enhance the immunogenicity of DOX, we prepare a reactive oxygen species (ROS)-responsive self-immolative polymer (R-SIP) that can efficiently destroy redox homeostasis via self-immolation-mediated glutathione depletion in cancer cells. Owing to its amphiphilic nature, R-SIP self-assemble into nano-sized particles under aqueous conditions, and DOX is efficiently encapsulated inside the nanoparticles by a simple dialysis method. Interestingly, when treated with 4T1 cancer cells, DOX-encapsulated R-SIP (DR-SIP) induces the phosphorylation of eukaryotic translation initiation factor 2 alpha and overexpression of ecto-calreticulin, resulting in endoplasmic reticulum-associated ICD. In addition, DR-SIP contributes to the maturation of dendritic cells by promoting the release of damage-associated molecular pat-terns (DAMPs) from cancer cells. When intravenously administered to tumor-bearing mice, DR-SIP remarkably inhibits tumor growth compared with DOX alone. Overall, DR-SIP may have the potential to elicit an immune response as an ICD inducer.
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