윤빈 (성균관대학교)

한빛사논문

조회254

윤빈Been Yoon

성균관대학교

Biomaterials, 2023 Apr;295:1220 | https://doi.org/10.1016/j.biomaterials.2023.122064 Self-immolative polymer-based immunogenic cell death inducer for regulation of redox homeostasis

Jueun Jeon^a,1, Been Yoon ^a,1, Anup Dey ^a, Seok Ho Song ^a, Yuce Li ^a, Hyeyeon Joo ^a, Jae Hyung Park a,b,c

^aSchool of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
^bDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University, Seoul 06351, Republic of Korea
^cBiomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea

¹These authors contributed equally.
Corresponding author : Jae Hyung Park

Abstract

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 2α 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 patterns (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.

논문정보

형식Research article
게재일2023년 04월 (BRIC 등록일 2023-04-26)
연구진국내 연구진
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