Evaluation of a Synthetic Polyethyleneimine Based Polymeric Vector for Gene Delivery to MCF-7 Breast Cancer Cells.

Objectives: Breast cancer is the most common type of cancer among women and the second most common cause of death after lung cancer. The inhibitor of growth (ING) transcript levels are often suppressed in cancer cells, making it a promising candidate for cancer therapy. In this study, we aimed to formulate a polyplex that effectively carries and delivers pING4 to breast cancer cells.

Exploring the Potential of siRNA Delivery in Acute Myeloid Leukemia for Therapeutic Silencing.

We investigated the feasibility of using siRNA therapy for acute myeloid leukemia (AML) by developing macromolecular carriers that facilitated intracellular delivery of siRNA. The carriers were derived from low-molecular-weight (<2 kDa) polyethyleneimine (PEI) and modified with a range of aliphatic lipids. We identified linoleic acid and lauric acid-modified PEI as optimal carriers for siRNA delivery to AML cell lines KG1 and KG1a, as well as AML patient-derived mononuclear cells.

Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers.

Chemically modified mRNA (modRNA) has proven to be a versatile tool for the treatment of various cancers and infectious diseases due to recent technological advancements. However, a safe and effective delivery system to overcome the complex extracellular and intracellular barriers is required in order to achieve higher therapeutic efficacy and broaden clinical applications. Here, we explored All-Fect and Leu-Fect C as novel transfection reagents derived from lipopolymers, which demonstrated excellent biocompatibility, efficient delivery capabilities, and a robust ability to escape the lysosomes.

Linoleic-acid-substituted polyethylenimine to silence heat shock protein 90B1 (HSP90B1) to inhibit migration of breast cancer cells.

Introduction: Breast cancer continues to be one of the leading causes of death in women, and the lack of treatment options for distant metastasis warrants the need to identify and develop more effective approaches. The aim of this study was to identify and validate targets that are associated with the survival and migration of the breast cancer cells in vitro through RNA interference (RNAi) approach.

Methods: Linoleic-acid-modified polyethylenimine (PEI) polymer was used to screen a short interfering RNA (siRNA) library against numerous cell adhesion and cytoskeleton genes in MDA-MB-231 triple-negative breast cell line, and the functional outcome of silencing was determined by growth and migration inhibition with further target validation studies.

Polymeric siRNA delivery targeting integrin-β1 could reduce interactions of leukemic cells with bone marrow microenvironment.

Uncontrolled proliferation of the myeloid cells due to fusion has been successfully treated with tyrosine kinase inhibitors (TKIs), which improved the survival rate of Chronic Myeloid Leukemia (CML) patients. However, due to interactions of CML cells with bone marrow microenvironment, sub-populations of CML cells could become resistant to TKI treatment. Since integrins are major cell surface molecules involved in such interactions, the potential of silencing integrin-β1 on CML cell line K562 cells was explored using short interfering RNA (siRNA) delivered through lipid-modified polyethyleneimine (PEI) polymers.

Enabling Combinatorial siRNA Delivery against Apoptosis-Related Proteins with Linoleic Acid and α-Linoleic Acid Substituted Low Molecular Weight Polyethylenimines.

Purpose: Short interfering RNA (siRNA) therapy promises a new era in treatment of breast cancers but effective delivery systems are needed for clinical use. Since silencing complementary targets may offer improved efficacy, this study was undertaken to identify non-viral carriers for combinatorial siRNA delivery for more effective therapy.

Methods: A library of lipid-substituted polymers from low molecular weight polyethyleneimine (PEI), linoleic acid (LA) and α-linoleic acid (αLA) with amide or thioester linkages was prepared and investigated for delivering Mcl-1, survivin and STAT5A siRNAs in breast cancer cells.

Novel targets for sensitizing breast cancer cells to TRAIL-induced apoptosis with siRNA delivery.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in variety of cancer cells without affecting most normal cells, which makes it a promising agent for cancer therapy. However, TRAIL therapy is clinically not effective due to resistance induction. To identify novel regulators of TRAIL that can aid in therapy, protein targets whose silencing sensitized breast cancer cells against TRAIL were screened with an siRNA library against 446 human apoptosis-related proteins in MDA-231 cells.

Polymeric Delivery of siRNA against Integrin-β1 (CD29) to Reduce Attachment and Migration of Breast Cancer Cells.

Cell surface integrins, which play important roles in the survival, proliferation, migration, and invasion of cancer cells, are a viable target for treatment of metastatic breast cancer. This line of therapy still remains challenging due to the lack of proper identification and validation of effective targets as well as the lack of suitable therapeutic agents for treatment. The focus is on one such molecular target for this purpose, namely integrin-β1, and effective lowering of integrin-β1 levels on a breast cancer model (MDA-MB-231 cells) is achieved by delivering a dicer-substrate short interfering RNA (siRNA) targeting integrin-β1 with lipid-modified low molecular weight polyethylenimine polymers.

Current attempts to implement siRNA-based RNAi in leukemia models.

Leukemias arise from genetic alterations in normal hematopoietic stem or progenitor cells, leading to abnormal blood population with transformed cells. With the advent of RNAi and its pharmacological mediator siRNA, it has become possible to downregulate specific drivers causing leukemias. In this review, we present unique aspects of RNAi-mediated therapy and delivery technologies.

Fibronectin-modified surfaces for evaluating the influence of cell adhesion on sensitivity of leukemic cells to siRNA nanoparticles.

Aim: This study aimed to create fibronectin (FN)-grafted polymeric surfaces to investigate the influence of leukemic cell adhesion on siRNA treatment.

Materials & Methods: FN was grafted on plasma-treated PTFE surfaces using chemical crosslinkers. Adhesion and growth of chronic myeloid leukemia K562 cells on modified surfaces were investigated.

Small hydrophobe substitution on polyethylenimine for plasmid DNA delivery: Optimal substitution is critical for effective delivery.

Unlabelled: Cationic polymers have been turned into effective gene delivery agents by functionalizing with long-chain aliphatic lipids, but little information exists if small hydrophobic moieties can serve as effective substituents for this purpose. To explore this issue, we modified small molecular weight (1.2kDa) polyethylenimine (1.

A Delicate Balance When Substituting a Small Hydrophobe onto Low Molecular Weight Polyethylenimine to Improve Its Nucleic Acid Delivery Efficiency.

High molecular weight (HMW) polyethylenimine (PEI) is one of the most versatile nonviral gene vectors that was extensively investigated over the past two decades. The cytotoxic profile of HMW PEI, however, encouraged a search for safer alternatives. Because of lack of cytotoxicity of low molecular weight (LMW) PEI, enhancing its performance via hydrophobic modifications has been pursued to this end.

Additive nanocomplexes of cationic lipopolymers for improved non-viral gene delivery to mesenchymal stem cells.

It has been challenging to modify primary cells with non-viral gene delivery. Herein, we developed a ternary nano-formulation for gene delivery to umbilical cord blood and bone marrow derived mesenchymal stem cells (MSC) by using lipid-modified small (1.2 kDa) molecular weight polyethylenimine (PEI1.

A comparative evaluation of disulfide-linked and hydrophobically-modified PEI for plasmid delivery.

Non-viral gene therapy has become an important approach for treatment of hereditary and acquired diseases as a result of better understanding of molecular mechanisms involved in disease development. To design more effective gene carriers, plasmid DNA (pDNA) delivery to 293T cells was investigated by using two types of polymeric carriers; polymer constructed with disulfide (-S-S-) linkages and polymers modified with hydrophobic moieties. The base polymer used for this study was 2-kDa poly(ethylene imine) (PEI2), a relatively cell-compatible but ineffective gene carrier.

Stabilization of gold nanoparticles by hydrophobically-modified polycations.

Surface-modified gold nanoparticles have pronounced benefits in the biomedical field due to their significant interaction with delivery materials. In the present study we used hydrophobically-modified polycations (i.e.