A novel micelleplex for tumour-targeted delivery of CRISPR-Cas9 against KRAS-mutated lung cancer.

CRISPR-Cas9 has emerged as a highly effective and customizable genome editing tool, holding significant promise for the treatment of KRAS mutations in lung cancer. In this study, we introduce a novel micelleplex, named C14-PEI, designed to co-deliver Cas9 mRNA and sgRNA efficiently to excise the mutated KRAS allele in lung cancer cells. C14-PEI is synthesised from 1,2-epoxytetradecane and branched PEI 600 Da a ring-opening reaction.

Cellular EMT-status governs contact guidance in an electrospun TACS-mimicking model.

In this study, an advanced nanofiber breast cancer model was developed and systematically characterized including physico-chemical, cell-biological and biophysical parameters. Using electrospinning, the architecture of tumor-associated collagen signatures (TACS5 and TACS6) was mimicked. By employing a rotating cylinder or static plate collector set-up, aligned fibers (TACS5-like structures) and randomly orientated fibers (TACS6-like structures) fibers were produced, respectively.

Endosomal escape mechanisms of extracellular vesicle-based drug carriers: lessons for lipid nanoparticle design.

The rise of biologics and RNA-based therapies challenges the limitations of traditional drug treatments. However, these potent new classes of therapeutics require effective delivery systems to reach their full potential. Lipid nanoparticles (LNPs) have emerged as a promising solution for RNA delivery, but endosomal entrapment remains a critical barrier.

Anionic polymer coating for enhanced delivery of Cas9 mRNA and sgRNA nanoplexes.

Polymeric carriers have long been recognized as some of the most effective and promising systems for nucleic acid delivery. In this study, we utilized an anionic di-block co-polymer, PEG-PLE, to enhance the performance of lipid-modified PEI (C14-PEI) nanoplexes for delivering Cas9 mRNA and sgRNA targeting KRAS G12S mutations in lung cancer cells. Our results demonstrated that PEG-PLE, when combined with C14-PEI at a weight-to-weight ratio of 0.

Diving into RNAi Therapy: An Inhalable Formulation Based on Lipid-Polymer Hybrid Systems for Pulmonary Delivery of siRNA.

Here, a pulmonary formulation based on lipid-polymer hybrid nanoparticles carrying small interfering RNA (siRNA) was developed to realize a RNA interference-based therapy to treat respiratory diseases. Toward this aim, a new copolymer was synthesized, by functionalization of the α,β-poly(-2-hydroxyethyl)-d,l-aspartamide with 35 mol % of 1,2-bis(3-aminopropylamino)ethane, 0.4 mol % of fluorescent dye, and 4.