PLA-PEG from PolySciTech used in development of bronchial-targetting particles for cystic fibrosis therapy

 

Cystic fibrosis is the second most common lethal inherited disorder related to a specific mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The potential for gene-editing may provide a treatment for this incurable disase. Recently, researchers at Yale University used PEG-PLA (cat# AK054) from PolySciTech (www.polyscitech.com) to test the effect of nanoparticle decorations on bronchial uptake from an inhaled formulation. This research holds promise to improve treatments against cystic fibrosis in the future. Read more: Luks, Valerie L., Hanna Mandl, Jenna DiRito, Christina Barone, Mollie R. Freedman-Weiss, Adele S. Ricciardi, Gregory G. Tietjen, Marie E. Egan, W. Mark Saltzman, and David H. Stitelman. "Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells." PloS one 17, no. 4 (2022): e0266218. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266218

“Abstract: Background: Advances in Molecular Therapy have made gene editing through systemic or topical administration of reagents a feasible strategy to treat genetic diseases in a rational manner. Encapsulation of therapeutic agents in nanoparticles can improve intracellular delivery of therapeutic agents, provided that the nanoparticles are efficiently taken up within the target cells. In prior work we had established proof-of-principle that nanoparticles carrying gene editing reagents can mediate site-specific gene editing in fetal and adult animals in vivo that results in functional disease improvement in rodent models of β-thalassemia and cystic fibrosis. Modification of the surface of nanoparticles to include targeting molecules (e.g. antibodies) holds the promise of improving cellular uptake and specific cellular binding. Methods and findings: To improve particle uptake for diseases of the airway, like cystic fibrosis, our group tested the impact of nanoparticle surface modification with cell surface marker antibodies on uptake in human bronchial epithelial cells in vitro. Binding kinetics of antibodies (Podoplanin, Muc 1, Surfactant Protein C, and Intracellular Adhesion Molecule-1 (ICAM)) were determined to select appropriate antibodies for cellular targeting. The best target-specific antibody among those screened was ICAM antibody. Surface conjugation of nanoparticles with antibodies against ICAM improved cellular uptake in bronchial epithelial cells up to 24-fold. Conclusions: This is a first demonstration of improved nanoparticle uptake in epithelial cells using conjugation of target specific antibodies. Improved binding, uptake or specificity of particles delivered systemically or to the luminal surface of the airway would potentially improve efficacy, reduce the necessary dose and thus safety of administered therapeutic agents. Incremental improvement in the efficacy and safety of particle-based therapeutic strategies may allow genetic diseases such as cystic fibrosis to be cured on a fundamental genetic level before birth or shortly after birth.”