Delivery of magnetic nanoparticles to lung cancer cells via polarized macrophages: A riveting tale of a bio-inspired phenomenon

•Molecular Interplay of Iron and Macrophages tumor microenvironment.•Macrophages and iron homeostasis inside the tumor Microenvironment.•Mechanism of tumor suppression via iron-loaded macrophages.•In-Vitro Internalization of iron nanoparticles and release inside the tumor microenvironment.•Development and internalization of ferromagnetic nanoparticles in AMs. Macrophages critically influences the tumor progression. The bio-carriers like macrophages have proven successful in circumventing this mammoth challenge by selectively infiltrating cancerous cells with anticancer drugs. Moreover, macrophage phenotypes have been found to have a key role in early phage of angiogenesis in the lungs. Phenotypic macrophages will serve to billet the iron, which has been found to have cancer cell-killing proficiency. Recent studies have shown the modulation of the molecular mechanism for tumor suppression by iron oxide (IO) nanoparticles. In addition, previous research focus on the interlink connections of iron and macrophages concerning macrophage polarization and consequent tumor suppression. However, we found that the initiation of the molecular response by external macrophages carrying anticancer agents has an exceptional breach in current drug delivery technology. We assume that macrophages carrying IO nanoparticles prepared by insemination-like formulation strategy to initiate the three-way response 1) directly invading the tumors with in vitro polarized macrophages; 2) Simultaneously delivering IO nanoparticles to augment the tumor suppression, and 3) IO deposition in TME further encourages polarization from M2 to proinflammatory M1 macrophages. Therefore, in the present study, we hypothesize that magnetic nanoparticles that are entrapped in phenotypic polarized macrophages will have striking potential to target lung cancer. In this hypothesis, we discussed the molecular interplay of iron and macrophages, in-vitro internalization of iron nanoparticles, and in vivo release inside the tumor cell.