دورية أكاديمية
Dual Targeted Nanoparticles for the Codelivery of Doxorubicin and siRNA Cocktails to Overcome Ovarian Cancer Stem Cells
| العنوان: | Dual Targeted Nanoparticles for the Codelivery of Doxorubicin and siRNA Cocktails to Overcome Ovarian Cancer Stem Cells |
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| المؤلفون: | Li Chen, Jinlan Luo, Jingyuan Zhang, Siyuan Wang, Yang Sun, Qinying Liu, Cui Cheng |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 14, p 11575 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | iRGD peptides, siRNAs, cancer stem cells, reduction sensitive, targeted delivery, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Most anticancer treatments only induce the death of ordinary cancer cells, while cancer stem cells (CSCs) in the quiescent phase of cell division are difficult to kill, which eventually leads to cancer drug resistance, metastasis, and relapse. Therefore, CSCs are also important in targeted cancer therapy. Herein, we developed dual-targeted and glutathione (GSH)-responsive novel nanoparticles (SSBPEI–DOX@siRNAs/iRGD–PEG–HA) to efficiently and specifically deliver both doxorubicin and small interfering RNA cocktails (siRNAs) (survivin siRNA, Bcl-2 siRNA and ABCG2 siRNA) to ovarian CSCs. They are fabricated via electrostatic assembly of anionic siRNAs and cationic disulfide bond crosslinking-branched polyethyleneimine-doxorubicin (SSBPEI–DOX) as a core. Interestingly, the SSBPEI–DOX could be degraded into low-cytotoxic polyethyleneimine (PEI). Because of the enrichment of glutathione reductase in the tumor microenvironment, the disulfide bond (–SS–) in SSBPEI–DOX can be specifically reduced to promote the controlled release of siRNA and doxorubicin (DOX) in the CSCs. siRNA cocktails could specifically silence three key genes in CSCs, which, in combination with the traditional chemotherapy drug DOX, induces apoptosis or necrosis of CSCs. iRGD peptides and “sheddable” hyaluronic acid (HA) wrapped around the core could mediate CSC targeting by binding with neuropilin-1 (NRP1) and CD44 to enhance delivery. In summary, the multifunctional delivery system SSBPEI–DOX@siRNAs/iRGD–PEG–HA nanoparticles displays excellent biocompatibility, accurate CSC-targeting ability, and powerful anti-CSC ability, which demonstrates its potential value in future treatments to overcome ovarian cancer metastasis and relapse. To support this work, as exhaustive search was conducted for the literature on nanoparticle drug delivery research conducted in the last 17 years (2007–2023) using PubMed, Web of Science, and Google Scholar. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/14/11575; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms241411575 |
| URL الوصول: | https://doaj.org/article/0ea82f22628b47be845ca447510a0f72 |
| رقم الأكسشن: | edsdoj.0ea82f22628b47be845ca447510a0f72 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms241411575 |