LNP-miR-155 cy5 Inhibitor Regulates the Copper Transporter via the β-Catenin/TCF4/SLC31A1 Signal for Colorectal Cancer Therapy

Abstract

Lipid nanoparticle (LNP) delivery systems are widely used in the delivery of small-molecule drugs and nucleic acids. In this study, we prepared LNP-miR-155 by lipid nanomaterial technology and investigated the effects of LNP-miR-155 on βcatenin/transcription factor 4 (TCF4)/solute carrier family 31 member 1/copper transporter 1 (SLC31A1/CTR1) signaling and copper transport in colorectal cancer. For this, we used an LNP-miR-155 cy5 inhibitor and LNP-miR-155 cy5 mimics for the transfection of HT-29/SW480 cells. The transfection efficiency and uptake efficiency were detected by immunofluorescence. Relevant cell assays confirmed that the LNP-miR-155 cy5 inhibitor mediates the regulation of copper transport through the βcatenin/TCF4/SLC31A1 axis. The LNP-miR-155 cy5 inhibitor reduced cell proliferation, migration, and colony formation and promoted cell apoptosis. We also confirmed that miR-155 downregulates HMG box-containing protein 1 (HBP1) and adenomatous polyposis coli (APC) in cells and activates the function of β-catenin/TCF4 signaling. In addition, we found that the copper transporter, SLC31A1, is highly expressed in colorectal cancer cells. Furthermore, we also found that the complex β-catenin/TCF4 promotes the transcription of SLC31A1 by binding to its promoter region, which sustains the transport of copper from the extracellular region to the intracellular region and increases the activities of Cu 2+ -ATPase and superoxide dismutase (SOD). In summary, the LNP-miR-155 cy5 inhibitor regulates β-catenin/TCF4 by downregulating SLC31A1-mediated copper transport and intracellular copper homeostasis.

Tumor Cell Lysate-Based Multifunctional Nanoparticles Facilitate Enhanced mRNA Delivery and Immune Stimulation for Melanoma Gene Therapy

“…To verify the cell proliferation inhibition capacity of the Bim mRNA, B16 cells were incubated in six-well plates at a density of 1 × 10 3 cells. , After 24 h, the B16 cells were transfected with the MLSV/Bim (4 μg) complex. Next, the cells were cultured and formed colonies in 1–2 weeks.…”

Combination of miR159 Mimics and Irinotecan Utilizing Lipid Nanoparticles for Enhanced Treatment of Colorectal Cancer

“…LNPs present distinct advantages in enhancing the pharmacokinetic properties and tissue distribution of therapeutic agents. Whether derived from natural or synthetic lipids, LNPs showcase outstanding biocompatibility and degradability [ 22 , 23 ]. In addition, LNPs also possess the ability to co-deliver multiple drugs and protect nucleic acid drugs from degradation.…”