Magnetically responsive PLGA-magnetite nanoparticles for in vitro stent targeting and delivery of therapeutic agents.

Coronary artery disease presents as an obstruction to coronary blood flow due to the presence of a vascular lesion. Treatment options include percutaneous transluminal coronary angioplasty and the deployment of a vascular stent to keep the artery open. However, in-stent restenosis can still occur because of neointimal hyperplasia driven by the accumulation of vascular smooth muscle cell (VSMC)-like cells within the stented vessel segment. Drug-eluting stents (DES) reduce restenosis by locally releasing anti-proliferative agents. Yet, current DES platforms are limited by fixed drug loading at implantation and the inability to replenish the drug at the stent after depletion. Here, we developed a magnetically responsive nanoparticle platform as a proof-of-concept strategy for targeted stent drug reloading. Poly (lactic-co-glycolic acid) magnetite nanoparticles (PLGA-MNPs) were engineered to encapsulate paclitaxel or the γ-secretase inhibitors, DAPT and Compound E. Nanoparticles were characterised by dynamic light scattering, electron microscopy, and inductively coupled plasma atomic emission spectroscopy. Their ability to bind stainless steel stents, release drugs, and modulate cellular responses was examined in vitro. PLGA-MNPs exhibited a mean hydrodynamic diameter of ∼215 nm with low polydispersity and stable suspension properties. Fluorescence imaging demonstrated increased retention of FITC-labelled PLGA-MNPs on stainless steel stents in the presence of a static magnetic field. Paclitaxel-loaded PLGA-MNPs inhibited murine mesenchymal stem cell proliferation, with enhanced efficacy observed under magnetic field exposure. Similarly, γ-secretase inhibitor-loaded PLGA-MNPs attenuated Jagged-1-induced expression of myogenic and Notch-responsive genes in vitro. Drug release from PLGA-MNPs was increased in the presence of a magnetic field over extended incubation periods. Notably, exposure to a static magnetic field alone also influenced gene expression, indicating that magnetic field effects must be considered when interpreting biological outcomes. Collectively, these findings demonstrate the feasibility of magnetically responsive PLGA-MNPs as a stent-targeted drug delivery platform. Further studies under physiological flow conditions and in vivo vascular injury models will be required to establish safety, targeting efficiency, and therapeutic efficacy.