Tumor-Targeting, MicroRNA-Silencing Porous Silicon Nanoparticles for Ovarian Cancer Therapy
Articolo
Data di Pubblicazione:
2019
Citazione:
Tumor-Targeting, MicroRNA-Silencing Porous Silicon Nanoparticles for Ovarian Cancer Therapy / A. Bertucci, K.-. Kim, J. Kang, J.M. Zuidema, S.H. Lee, E.J. Kwon, D. Kim, S.B. Howell, F. Ricci, E. Ruoslahti, H.-. Jang, M.J. Sailor. - In: ACS APPLIED MATERIALS & INTERFACES. - ISSN 1944-8244. - 11:27(2019 Jul 10), pp. 23926-23937. [10.1021/acsami.9b07980]
Abstract:
Silencing of aberrantly expressed microRNAs (miRNAs or miRs) has emerged as one of the strategies for molecular targeted cancer therapeutics. In particular, miR-21 is an oncogenic miRNA overexpressed in many tumors, including ovarian cancer. To achieve efficient administration of anti-miR therapeutics, delivery systems are needed that can ensure local accumulation in the tumor environment, low systemic toxicity, and reduced adverse side effects. In order to develop an improved anti-miR therapeutic agent for the treatment of ovarian cancer, a nanoformulation is engineered that leverages biodegradable porous silicon nanoparticles (pSiNPs) encapsulating an anti-miR-21 locked nucleic acid payload and displaying a tumor-homing peptide for targeted distribution. Targeting efficacy, miR-21 silencing, and anticancer activity are optimized in vitro on a panel of ovarian cancer cell lines, and a formulation of anti-miR-21 in a pSiNP displaying the targeting peptide CGKRK is identified for in vivo evaluation. When this nanoparticulate agent is delivered to mice bearing tumor xenografts, a substantial inhibition of tumor growth is achieved through silencing of miR-21. This study presents the first successful application of tumor-targeted anti-miR porous silicon nanoparticles for the treatment of ovarian cancer in a mouse xenograft model.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
cancer therapy; COV-318 ovarian cancer xenograft; in vivo; locked nucleic acid; microRNA silencing; miR-21; nanomedicine; peptide targeting; Animals; Cell Line, Tumor; Female; Humans; Mice; Mice, Nude; Porosity; Xenograft Model Antitumor Assays; Drug Carriers; MicroRNAs; Nanoparticles; Ovarian Neoplasms; Silicon
Elenco autori:
A. Bertucci, K.-. Kim, J. Kang, J.M. Zuidema, S.H. Lee, E.J. Kwon, D. Kim, S.B. Howell, F. Ricci, E. Ruoslahti, H.-. Jang, M.J. Sailor
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