Therapeutic potential of a cell penetrating peptide (CPP, NP1) mediated siRNA delivery: Evidence in 3D spheroids of colon cancer cells

Abstract

RNA interference holds great potential for cancer therapeutics and its success is highly dependent on an effective delivery system. As most preclinical drug screening in vitro was conducted in flat monolayer cell cultures, development of more physiologically relevant models is needed to enhance testing reliability and effectiveness. Here, the aim was to develop 3D cell spheroids and evaluate the efficiency of NP1, a novel cell penetrating peptide, CPP (STR-H16R8), developed by our group to assist siRNA delivery. NP1 elicited significant cellular uptake of siRNA and promoted great siRNA knockdown efficiency of Bcl-2 and VEGF mRNA in 3D spheroids (53% and 51%, respectively), induced marked apoptosis after silencing HIF mRNA, and 3D spheroids displayed apoptosis resistance compared to 2D cells. Taken together, 3D spheroids provide an improved model for testing siRNA delivery and NP1 has proved to be a powerful in vitro transfection reagent. K E Y W O R D S3D spheroids, apoptosis, colon cancer, gene therapy, siRNA delivery

Designing Cell Delivery Peptides and SARS-CoV-2-Targeting Small Interfering RNAs: A Comprehensive Bioinformatics Study with Generative Adversarial Network-Based Peptide Design and In Vitro Assays

“…Here, we hypothesize that the final siRNA sequence database composed of 62 sequences could target the SARS-CoV-2 genome in several genes of interest. As previously mentioned, delivery peptides have been used to help the intracellular delivery of active molecules, such as siRNA, thus we hypothesize that our siRNAs could be delivery to cells by using covalently attached CPPs, as described in detail in reviews such as the one by Beloor et al …”

“…Here, we hypothesize that the final siRNA sequence database composed of 62 sequences could target the SARS-CoV-2 genome in several genes of interest. As previously mentioned, delivery peptides have been used to help the intracellular delivery of active molecules, such as siRNA, 45 thus we hypothesize that our siRNAs could be delivery to cells by using covalently attached CPPs, as described in detail in reviews such as the one by Beloor et al 46 Designed Cell-Penetrating Peptides. By controlling the probability distribution of the new peptide sequences, the deep learning GAN method allowed for the sorting of those sequences into positive (CPP) and negative (non-CPP) classes, considering physicochemical descriptors such as charge, hydrophobicity, and molecular weight of the data from which it learned.…”

Peptide-Functionalized Nanoparticles-Encapsulated Cyclin-Dependent Kinases Inhibitor Seliciclib in Transferrin Receptor Overexpressed Cancer Cells

“…The application of CPPs in cancer therapy has drawn lots of attention in areas including triple-negative breast cancer, ovarian cancer, colorectal cancer etc. [ 20 , 21 , 22 ]. Recently, the cationic Tat-peptide modified nanoformulations have been demonstrated to deliver antiviral drugs as well as vaccines for treatment of SARS-CoV-2 infections [ 23 ].…”

A perspective on The Canadian Journal of Chemical Engineering commemorating its 100th volume: 1929–2021

“…Year Title, theme, or topic Affiliation of principal organizer(s) Process Control [79] University of British Columbia Laval University Biomedical Engineering [80] McGill University Multiphase Computational Fluid Dynamics for Industrial Processes [81] Schlumberger DBR Technology Center University of Alberta Nanotechnology [82] University of Waterloo Highlights on Chemical Engineering Research in Latin America [83] Universidade Federal do Rio de Janeiro Chemical Reaction Engineering [84] University of British Columbia Catalysis [85] University of Houston Oil Sands Technology [86] University of Alberta Advances in Fundamental Research and Application Development of Cellulose Nanocrystals [87] University of British Columbia FPInnovations Voices from China [88] Shandong University of Science and Technology Experimental Methods in Chemical Engineering [89] Polytechnique Montreal Experimental Methods in Chemical Engineering-Virtual Issue [90] Polytechnique Montreal Established Leaders in Chemical Engineering [91] CJCE/University of Alberta Emerging Leaders in Chemical Engineering [92] CJCE/University of Alberta Carbon nanotube/ZnO nanowire/polyvinylidene fluoride hybrid nanocomposites for enhanced electromagnetic interference shielding [108] U. Sundararaj University of Calgary Therapeutic potential of a cell penetrating peptide (CPP, NP1) mediated siRNA delivery: Evidence in 3D spheroids of colon cancer cells [109] P. Chen A. Elkamel University of Waterloo Polymer branching and first normal stress differences in small-amplitude oscillatory shear flow [110] A. J. Giacomin Queen's University Intermittent ultrasound-assisted ceramic membrane fouling control in ultrafiltration [111] H. Doan Ryerson University Rheology and processing of polytetrafluoroethylene (PTFE) paste [112] S. G. Hatzikiriakos UBC Sustainable management and design of the energy-water-food nexus using a mathematical programming approach [113] A. Almansoori, A. Elkamel Khalifa UST, University Waterloo High-performance photocatalysts for the selective oxidation of alcohols to carbonyl compounds [114] R. Farnood University of Toronto A review of heat-transfer mechanism for solid deposition from 'waxy' or paraffinic mixtures [115] A. K. Mehrotra University of Calgary Design of polymeric materials: Experiences and prescriptions [116] A. Penlidis University of Waterloo Sustai...…”