Polymer nanoparticles mediated codelivery of antimiR-10b and antimiR-21 for achieving triple negative breast cancer therapy.

Abstract

The current study shows the therapeutic outcome achieved in triple negative breast cancer (TNBC) by simultaneously antagonizing miR-21-induced antiapoptosis and miR-10b-induced metastasis, using antisense-miR-21-PS and antisense-miR-10b-PS delivered by polymer nanoparticles (NPs). We synthesized the antisense-miR-21 and antisense-miR-10b loaded PLGA-b-PEG polymer NPs and evaluated their cellular uptake, serum stability, release profile, and the subsequent synchronous blocking of endogenous miR-21 and miR-10b function in TNBC cells in culture, and tumor xenografts in living animals using molecular imaging. Results show that multitarget antagonization of endogenous miRNAs could be an efficient strategy for targeting metastasis and antiapoptosis in the treatment of metastatic cancer. Targeted delivery of antisense-miR-21 and antisense-miR-10b coloaded urokinase plasminogen activator receptor (uPAR) targeted polymer NPs treated mice showed substantial reduction in tumor growth at very low dose of 0.15 mg/kg, compared to the control NPs treated mice and 40% reduction in tumor growth compared to scramble peptide conjugated NPs treated mice, thus demonstrating a potential new therapeutic option for TNBC.

• Authors: Rammohan Devulapally, Narayana M Sekar, Thillai V Sekar, Kira Foygel, Tarik F Massoud, Jürgen K Willmann, Ramasamy Paulmurugan
• Journal: ACS nano (ACS Nano) Vol. 9 Issue 3 Pg. 2290-302 (Mar 24 2015) ISSN: 1936-086X [Electronic] United States
• PMID: 25652012 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Carriers
• MIRN10 microRNA, human
• MIRN21 microRNA, human
• MicroRNAs
• Receptors, Urokinase Plasminogen Activator
• poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
• Polyglactin 910
• Polyethylene Glycols

Topics

• Animals
• Biological Transport
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (genetics)
• Cell Transformation, Neoplastic
• Drug Carriers (chemistry)
• Female
• Genetic Therapy
• Humans
• Mice
• MicroRNAs (chemistry, genetics, metabolism)
• Nanomedicine (methods)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Polyethylene Glycols (chemistry)
• Polyglactin 910 (chemistry)
• RNA Stability
• Receptors, Urokinase Plasminogen Activator (genetics)
• Triple Negative Breast Neoplasms (genetics, pathology, therapy)