3.1.2. Heparin-Coated Metal NanoParticles

Another important direction is the development of targeted delivery systems based on magnetic metal nanoparticles. The main disadvantage of such nanomaterials is that we need to select a proper stabilizer or coating that will contribute to the constant particle size, reduce their toxic effects, increase biocompatibility, and overcome physiological barriers maintaining their high magnetic properties. Hep was found to be a sound basis for these coatings [131]. Another study demonstrated that with Hep's utilization, it is possible to create stable magnetic nanoparticles, based on iron oxide, exhibiting low polydispersity [132]. The introduction of cis-platin to the composition of Hep and iron oxide created Hep-coated metal nanoparticles, which exhibited a cytotoxic effect on cancer cells but lowered toxic side- effects compared to the free drug [133].

In similar studies, magnetic nanoparticles were modified with polyethylene glycol (PEG) and Hep, after which they were functionalized with additional targeting agents. PE-Gylation enables longer circulation time but can also render metal nanoparticles increased passive targeting via the EPR effect. PEGylated metal nanoparticles were, furthermore, modified with a Hep layer to enable the carrying of the highly cationic CPP-linked protein drug [134]. Further studies demonstrated that the resulting nanoparticles have an increased recirculation time in the blood, retain their high magnetic properties, and overcome the BBB. It was also shown that in a mouse 9L glioma model, particles with a size of more than 50 nm accumulate at high concentrations in the tumor tissues [135].
