title: Apoptosis induction and attenuation of inflammatory gene expression in murine macrophages via multitherapeutic nanomembranes.
abstract: The realization of optimized therapeutic delivery is impaired by the challenge of localized drug activity and by the dangers of systemic cytotoxicity which often contribute to patient treatment complications. Here we demonstrate the block copolymer-mediated deposition and release of multiple therapeutics which include an LXRα/β agonist 3-((4-methoxyphenyl)amino)-4-phenyl-1-(phenylmethyl)-1H-pyrrole-2,5-dione (LXRa) and doxorubicin hydrochloride (Dox) at the air-water interface via Langmuir-Blodgett deposition, as well as copolymer-mediated potent drug elution toward the Raw 264.7 murine macrophage cell line. The resultant copolymer-therapeutic hybrid serves as a localized platform that can be functionalized with virtually any drug due to the integrated hydrophilic and hydrophobic components of the polymer structure. In addition, the sequestering function of the copolymer to anchor the drugs to implant surfaces can enhance delivery specificity when compared to systemic drug administration. Confirmation of drug functionality was confirmed via suppression of the interleukin 6 (Il-6) and tumor necrosis factor alpha (TNFα) inflammatory cytokines (LXRa), as well as DNA fragmentation analysis (Dox). Furthermore, the fragmentation assays and gene expression analysis demonstrated the innate biocompatibility of the copolymeric material at the gene expression level via the confirmed absence of material-induced apoptosis and a lack of inflammatory gene expression. This modality enables layer-by-layer control of agonist and chemotherapeutic functionalization at the nanoscale for the localization of drug dosage, while simultaneously utilizing the copolymer platform as an anchoring mechanism for drug sequestering, all with an innate material thickness of 4 nm per layer, which is orders of magnitude thinner than existing commercial technologies. Furthermore, these studies comprehensively confirmed the potential translational applicability of copolymeric nanomaterials as localized multitherapeutic thin film platforms.
authors.affiliation: Department of Biomedical Engineering, Robert R McCormick School of Engineering and Applied Science, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA. Department of Mechanical Engineering, Robert R McCormick School of Engineering and Applied Science, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Pierstorff
authors.forename: Max
authors.initials: M
authors.lastname: Krucoff
authors.forename: Dean
authors.initials: D
authors.lastname: Ho