Synergistic Silencing of Skp2 by siRNA Self-Assembled Nanoparticles as a Therapeutic Strategy for Advanced Prostate Cancer.
Small
; 18(14): e2106046, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35182014
ABSTRACT
Advanced prostate cancer, harboring multiple mutations of tumor suppressor genes, is refractory to conventional therapies. Knockout of the Skp2 gene blocks pRb/p53 doubly deficient prostate cancer in mice, which inspired the authors to develop an approach for delivering siRNA that would efficiently silence Skp2 (siSkp2) in vivo. Here, a facile strategy is reported to directly assemble siSkp2 with the natural compound quercetin (Que) into supramolecular nanoparticles (NPs). This carrier-free siSkp2 delivery system could effectively protect siSkp2 from degradation in serum and enhance its cellular internalization. Furthermore, the siSkp2/Que NPs exhibit synergistic effects in Skp2 silencing, because they can degrade the mRNA and protein of Skp2 simultaneously. Indeed, siSkp2/Que NPs remarkably diminish the Skp2 abundance and further inhibit the proliferation and migration of TMU cells (RB1/TP53/KRAS triple mutations) in vitro. The in vivo results further show that i.v. administration of siSkp2/Que NPs efficiently accumulates in tumor sites and strongly inhibits the growth of TMU tumors in nude mice. Importantly, the siSkp2/Que NPs do not induce any abnormality in the treated mice, which suggests satisfactory biocompatibility. Collectively, this study describes a tractable siRNA self-assembled strategy for Skp2 silencing, which might be a promising nanodrug to cure multitherapy-resistant advanced prostate cancer.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Nanopartículas
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article