Magnetic nanoparticles for targeted vascular delivery

Abstract

Magnetic targeting has shown promise to improve the efficacy and safety of different classes of therapeutic agents by enabling their active guidance to the site of disease and minimizing dissemination to nontarget tissues. However, its translation into clinic has proven difficult because of inherent limitations of traditional approaches inapplicable for deep tissue targeting in human subjects and a need for developing well-characterized and fully biocompatible magnetic carrier formulations. A novel magnetic targeting scheme based on the magnetizing effect of deep-penetrating uniform fields is presented as an example of a strategy providing a potentially clinically viable solution for preventing injury-triggered reobstruction of stented blood vessels (in-stent restenosis). The design of optimized magnetic carrier formulations and experimental results showing the feasibility of uniform field-controlled targeting for site-specific vascular delivery of small-molecule pharmaceuticals, biotherapeutics, and cells are discussed in the context of antirestenotic therapy. The versatility of this approach applicable to different classes of therapeutic agents exerting their antirestenotic effects through distinct mechanisms prompts exploring the utility of uniform field-mediated magnetic stent targeting for combination therapies with enhanced efficiencies and improved safety profiles. Additional improvements in terms of site specificity and protracted carrier retention at the site of injury may be expected from the development and use of magnetic carriers exhibiting affinity for arterial wall-specific antigens.

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

“…Dividing cells were shown to process MNPs many times faster than contact-inhibited cells, possibly as a result of the rapid cumulative expansion of the cytosol compartment promoting solubilization of the released oligomeric fragments and facilitating their diffusion from the particle matrix. Thus, in the therapeutic context of magnetically targeted drug or cell delivery as a therapeutic strategy for preventing arterial restenosis (35), our experiments offer several important observations. The increased rates of MNP disassembly in an acidified semisolid environment and in dividing smooth muscle cells suggest that the degradation of the respective fractions of the arterial wall-localized MNPs, i.e., those immobilized in the extracellular matrix or taken up by neointimal cells, may occur substantially faster early in the healing phase, characterized by rapid cell proliferation and inflammation, which may cause acidification of the local microenvironment (36).…”

Stimuli-responsive nanomaterials for therapeutic protein delivery

“…Magnetic targeting is based on two primary elements: a magnetic field source and a magnetically responsive drug carrier [111]. …”

Preparation of Ni0.5Zn0.5Fe2O4/SiO2 nanocomposites and their adsorption of bovine serum albumin

“…Now, the MNPs have been widely applied to biological and medical areas [3][4][5], such as drug and gene delivery [6,7], the control of cells and cellular function [8,9], therapeutic hyperthermia [10,11], bioseparation [12,13], magnetic resonance imaging [14][15][16][17], and quantitative immunoassay [18,19]. Beyond the biomedical area, interesting studies have been reported on the use of MNPs for ferrofluids, data storage, and catalysis [20].…”