Multitherapeutic hybrid material platforms for nanoengineered medicine

The realization of optimized therapeutic delivery is often challenged by the inability for localized drug activity and systemic cytotoxicity which can contribute to patient treatment complications. Here we demonstrate the block copolymer-mediated deposition of LXRalpha/beta 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. Confirmation of drug functionality was confirmed via suppression of the interleukin 6 (II-6) and tumor necrosis factor alpha (TNFalpha) inflammatory cytokines (LXRa), as well as DNA fragmentation analysis (Dox). Furthermore, the fragmentation assays demonstrated the innate biocompatibility of the copolymeric material at the genetic level via the confirmed absence of material-induced apoptosis. This modality enables layer-by-layer control of agonist and chemotherapeutic functionalization at the nanoscale for the fine tuning 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 multi-therapeutic thin film platforms.