Tumor-Targeting, MicroRNA-Silencing Porous Silicon Nanoparticles for Ovarian Cancer Therapy.

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.

• Authors: Alessandro Bertucci, Kang-Hoon Kim, Jinyoung Kang, Jonathan M Zuidema, Seo Hyeon Lee, Ester J Kwon, Dokyoung Kim, Stephen B Howell, Francesco Ricci, Erkki Ruoslahti, Hyeung-Jin Jang, Michael J Sailor
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 11 Issue 27 Pg. 23926-23937 (Jul 10 2019) ISSN: 1944-8252 [Electronic] United States
• PMID: 31251556 (Publication Type: Journal Article)

Chemical References

• Drug Carriers
• MIRN21 microRNA, human
• MicroRNAs
• Silicon

Topics

• Animals
• Cell Line, Tumor
• Drug Carriers (chemistry, pharmacology)
• Female
• Humans
• Mice
• Mice, Nude
• MicroRNAs (chemistry, genetics, pharmacology)
• Nanoparticles (chemistry, therapeutic use)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, pathology)
• Porosity
• Silicon (chemistry, pharmacology)
• Xenograft Model Antitumor Assays