2.2.3. Nanoparticles to Target Circulating Immune Cells

Before homing on diseased areas, nanomedicines can be recognized and interact with circulating immune cells in the bloodstream. In this case, immune cells loaded with nanomedicines become drug carriers, which significantly extend the circulation time of nanoparticles with broad-spectrum tumor-targeting properties. Interestingly, immune cells can cross many biological barriers and are natural carriers due to their homing characteristics (e.g., inflammatory sites, tumors). To do so, monocytes-macrophages, lymphocytes, and neutrophils might represent the most favorable options. Nevertheless, these cells are quite difficult to extract and are not necessarily optimal for drug delivery (e.g., low drug loading efficiency, changes in cell function after drug loading, and degradation of drugs by cellular enzymes).

According to the loading technique, immune cells are simply divided into two categories: "backpacks" (i.e., onto cells through adsorption, ligand-receptor interaction, and chemical coupling) and "Trojan horses" (i.e., into cells through hypotonic hemolysis, electroporation, membrane encapsulation, and phagocytosis). These different aspects have been extensively reviewed by Zhang et al. [44]. As an example, the Trojan horse strategy has been already used with monocytes as cellular vehicles for the co-transport of oxygen-loaded polymer bubbles/a photosensitizer (chlorin e6) and SPIONs to target hypoxic tumors with photodynamic therapy (PDT). Following activation by an external high-frequency magnetic field (HFMF), the co-entrapped SPIONs induced the thermal ablation of murine prostate (Tramp-C1 tumor-bearing mice) while inducing the release of oxygen available for the PDT effect [45].
