<p>Nanosized functional miRNA liposomes and application in the treatment of TNBC by silencing Slug gene</p>

Abstract

Background: Neo-adjuvant chemotherapy is an effective strategy for improving treatment of breast cancers. However, the efficacy of this treatment strategy is limited for treatment of triple negative breast cancer (TNBC). Gene therapy may be a more effective strategy for improving the prognosis of TNBC. Methods: A novel 25 nucleotide sense strand of miRNA was designed to treat TNBC by silencing the Slug gene, and encapsulated into DSPE-PEG 2000 -tLyp-1 peptide-modified functional liposomes. The efficacy of miRNA liposomes was evaluated on invasive TNBC cells and TNBC cancer-bearing nude mice. Furthermore, functional vinorelbine liposomes were constructed to investigate the anticancer effects of combined treatment. Results: The functional miRNA liposomes had a round shape and were nanosized (120 nm). Functional miRNA liposomes were effectively captured by TNBC cells in vitro and were target to mitochondria. Treatment with functional liposomes silenced the expression of Slug and Slug protein, inhibited the TGF-β1/Smad pathway, and inhibited invasiveness and growth of TNBC cells. In TNBC cancer-bearing mice, functional miRNA liposomes exerted a stronger anticancer effect than functional vinorelbine liposomes, and combination therapy with these two formulations resulted in nearly complete inhibition of tumor growth. Preliminary safety evaluations indicated that the functional miRNA liposomes did not affect body weight or cause damage to any major organs. Furthermore, the functional liposomes significantly increased the half-life of the drug in the blood of cancer-bearing nude mice, and increased drug accumulation in breast cancer tissues. Conclusion: In this study, we constructed novel functional miRNA liposomes. These liposomes silenced Slug expression and inhibited the TGF-β1/Smad pathway in TNBC cells, and enhanced anticancer efficacy in mice using combined chemotherapy. Hence, the present study demonstrated a promising strategy for gene therapy of invasive breast cancer.

A smart viral vector for targeted delivery of hydrophobic drugs

“…tLyP-1, chosen as a targeting peptide, is an active CendR peptide that binds to neuropilin receptors (NRP1 and NRP2) that are typically overexpressed in the angiogenic vessels of most malignant tumor cells and in the majority of carcinomas 36 . So far, tLyP-1 has been conjugated to a variety of nano-delivery vehicles based on metal 37 , 38 , mesoporous silica 39 , PEG-PLA 40 , non-ionic surfactants 41 , liposomes 42 , 43 and exosomes 44 . tLyP-1 has also been conjugated with molecular trackers 36 , 45 , with other peptides 46 , and co-administered with drug-polymer conjugates 47 – 49 .…”

Importance of microRNAs in Skin Oncogenesis and Their Suitability as Agents and Targets for Topical Therapy

“…Especially for variations with gold nanoparticles data are available [113]. Variations of liposomal structures have been validated for many years with regard to their suitability as drug delivery systems, also with regard to miRNA [114][115][116][117][118][119]. Only through the develop-DOI: 10.1159/000509879 ment of so-called transfersomes (ultra-deformable liposomes) could incorporated macromolecules such as peptides, DNA vaccines, and proteins be effectively transported transmembrane or transcorneally [120][121][122].…”

The Emerging Role of MicroRNAs in Breast Cancer

“…Single-stranded oligonucleotides with miRNA-complementary sequences are used to silence the miRNA function of target proteins. Functional miRNA liposomes have been developed to inhibit SLUG expression and the TGF- β 1/SMAD pathway in TNBC cells, and to enhance the efficacy of chemotherapy in mice [ 53 ]. Epigenetic strategies using histone deacetylase inhibitors or functionally cooperative miRNAs are effective approaches for eliminating HER3 signal transduction for BC treatment [ 54 ].…”