Cell uptake of magnetic nanoparticles

The recent advances in synthesis routes and functionalization of magnetic nanoparticles (NPs) have enabled new opportunities for scientific research in the field of biomedicine. The use of magnetic NPs can be already found in routine laboratory and clinical protocols, such as cell sorting, DNA separation, Magnetic Resonance Imaging (MRI) and gene therapy. Currently, eukaryotic cells can be easily targeted with magnetic nanoparticles of a given size, since the dimensions of such particles are comparable to any subcellular structure. However, the central question of how a given cell type recognizes and incorporates a passive nanoparticle is not yet completely understood. 

Current improvements in this field rely on new functionalization processes of the NPs with specific ligands for targeting specific cell membrane receptors. (Jaulin et al., 2000) The use of NPs for targeted delivery of anticancer agents and molecular diagnosis, developed along the last years, has been already reviewed in detail. Loading magnetic NPs with specific anticancer drugs and targeting them to specific tumor sites is a promising strategy for detection and elimination of neoplastic cells disregarding their physical size, which in turn could stop metastatic cells from proliferating. However, it is now generally recognized that the reticulo-endothelial system (RES) is a very effective system that detects and phagocytes NPs, preventing their therapeutic function. This high effectiveness make necessary for any system of NPs to be used as targeting carrier to mimic biological units in order to pass through the RES without being detected.

The use of charged cells as selective biological vectors for in vivo applications is a promising strategy to avoid the subtle problems related to the response of a living organism to alien objects (i.e., NPs-drug assembly). Specifically, the injection of nanoparticle-loaded DCs into the blood system appears as a valuable drug-delivery strategy for tumor targeting, since the cargo is delivered inside a known object (the DC cells) and therefore no RES action against these carriers is expected. DCs are the most potent antigen presenting cells to naive T-cells, triggering antigen-specific immune responses. These cells can be obtained from myeloid or plasmocitoid progenitors. DCs obtained from myelomonocytic progenitors (MDCs) and primed with tumor antigens have shown antitumoral activity when inoculated in animal models and human. Recently, the induction of endothelial cell features in MDCs cultured in the presence of angiogenic factors like VEGF has been demonstrated  and similar cells have been isolated from human tumor vessels, opening the possibility of targeting MDCs which have incorporated magnetic nanoparticles to tumor sites and use them to visualize tumors by magnetic resonance imaging (MRI) or for oncologic therapy: in this respect, magnetic inductive hyperthermia can effectively kill tumors to which sufficient numbers of nanoparticles have been delivered.

The importance of magnetic NPs for these applications is not only due to their role as passive carriers, but actually on their concurrent multi-tasking capacities such as a) having a magnetic core for location as MRI contrast agent; b) having power absorption capacity for drug release or hyperthermic ablation; or c) have porous surface to store specific drugs for long-term release by magnetic field stimulation. The efficiency of magnetic NPs for a given application will depend strongly on specific characteristics of the constituent material. An important property is related with high magnetic moment required in order to reduce the clinical doses and minimize possible toxicity effects.