DNA tetrahedral nanoparticles: Co-delivery of siOTUD6B/DOX against triple-negative breast cancer.

Autor: Zhang W; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Yang X; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Qu Z; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Ding P; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Kong X; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Wang X; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Liu Q; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Zhang X; Pooling Medical Research Institutes of 100Biotech, Beijing 100006, China., Lu Y; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China., Wang J; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: wangjing@cicams.ac.cn., Chen Z; Pooling Medical Research Institutes of 100Biotech, Beijing 100006, China. Electronic address: czj@pku.edu.cn., Fang Y; Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: fangyi0501@vip.sina.com.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2025 Jan 10; Vol. 377, pp. 197-211. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1016/j.jconrel.2024.11.025
Abstrakt: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited targeted therapeutic options. Recently, the deubiquitinizing enzyme ovarian tumor domain-containing 6B (OTUD6B) has been reported to play a potential role in TNBC progression. Therefore, this study investigates the role and underlying molecular mechanisms of OTUD6B in vitro and xenograft models of TNBC. Specifically, we examined the therapeutic effects of siOTUD6B and doxorubicin (DOX) co-delivery using synthesized tetrahedral DNA nanoparticles (Tds) on tumor growth and progression. Additionally, the uptake and efficacy of the siOTUD6B/DOX@Td in TNBC cells were evaluated. Notably, the siOTUD6B/DOX@Td nanoparticle demonstrated efficient cellular uptake by TNBC cells, resulting in OTUD6B knockdown and controlled release of DOX. Additionally, siOTUD6B/DOX@Td treatment enhanced apoptosis rates increased DOX sensitivity, and inhibited TNBC cell growth, migration, and metastasis. Moreover, in vivo experiments confirmed that siOTUD6B/DOX@Td treatment inhibited tumor growth and metastasis without damaging the primary organs. Mechanistically, OTUD6B regulates TNBC progression by stabilizing murine double minute 2 (MDM2) and degrading forkhead box O3a (FOXO3a). Conclusively, this study demonstrates the potential applicability of DNA nanoparticles loaded with DOX and siOTUD6B for TNBC treatment.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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