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RNA Micelles for Systemic Delivery of Anti-miRNA for Cancer Targeting and Inhibition without Ligand.

ACS Nano 2018 December 14
Displaying the advantage of nanoparticles in cancer targeting and drug delivery, micelles have shown great potential in cancer therapy. The mechanism for micelle targeting to cancer without the need of ligand is due to the size advantage of micelles within the lower end of the nanometer scale that is the optimal size favoring Enhanced Permeability and Retention (EPR) effect while escaping trapping by macrophages. MicroRNAs (miRNAs) are ubiquitous and play critical roles in regulating gene expression, cell growth and cancer development. However, its in vivo delivery in medical applications is still challenging. Here, we report the targeted delivery of anti-miRNA to cancers via RNA micelles. The phi29 packaging RNA three-way junction (pRNA-3WJ) was used as a scaffold to construct micelles. An oligo with 8nt locked nucleic acid (LNA) complementary to the seed region of miRNA21 was included in the micelles as an interference molecule for cancer inhibition. These RNA micelles carrying anti-miR21 exhibited strong binding and internalization to cancer cells, inhibited the function of oncogenic miR21, enhanced the expression of the pro-apoptotic factor, and induced cell apoptosis. Animal trials revealed effective tumor targeting and inhibition in xenograft model. Inclusion of folate as a targeting ligand in the micelles did not show significant improvement of the therapeutic efficacy in vivo, suggesting that micelles can carry therapeutics to target tumor and inhibit its growth without ligands.

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