Polymeric materials have been extensively explored in the field of nanomedicine; within them, poly lactic-co-glycolic acid (PLGA) holds a prominent position in micro- and nanotechnology due to its biocompatibility and controllable biodegradability. In this review we focus on the combination of PLGA with different inorganic nanomaterials in the form of nanocomposites to overcome the polymer’s limitations and extend its field of applications. We discuss their physicochemical properties and a variety of well-established synthesis methods for the preparation of different PLGA-based materials. Recent progress in the design and biomedical applications of PLGA-based materials are thoroughly discussed to provide a framework for future research.

Key Points: Heme and iron induce macrophage phenotypic switching toward an M1 proinflammatory phenotype. By scavenging free heme, hemopexin reverts heme-induced proinflammatory activation of macrophages in a mouse model of sickle cell disease.

Iron accumulates in human atherosclerotic lesions but whether it is a cause or simply a downstream consequence of the atheroma formation has been an open question for decades. According to the so called “iron hypothesis”, iron is believed to be detrimental for the cardiovascular system, thus promoting atherosclerosis development and progression. Iron, in its catalytically active form, can participate in the generation of reactive oxygen species and induce lipid-peroxidation, triggering endothelial activation, smooth muscle cell proliferation and macrophage activation; all of these processes are considered to be proatherogenic. On the other hand, the observation that hemochromatotic patients, affected by life-long iron overload, do not show any increased incidence of atherosclerosis is perceived as the most convincing evidence against the “iron hypothesis”. Epidemiological studies and data from animal models provided conflicting evidences about the role of iron in atherogenesis. Therefore more careful studies are needed in which issues like the source and the compartmentalization of iron will be addressed. This review article summarizes what we have learnt about iron and atherosclerosis from epidemiological studies, animal models and cellular systems and highlights the rather contributory than innocent role of iron in atherogenesis.

Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment. Here we identified a subset of iron-loaded, pro-inflammatory TAMs localized in hemorrhagic areas of the tumor microenvironment. The occurrence of iron-loaded TAMs (iTAMs) correlated with reduced tumor size in patients with non-small cell lung cancer. Ex vivo experiments established that TAMs exposed to hemolytic red blood cells were converted into pro-inflammatory macrophages capable of directly killing tumor cells. This anti-tumor effect could also be elicited via iron oxide nanoparticles. When tested in vivo, tumors injected with such iron oxide nanoparticles led to significantly smaller tumor sizes compared to controls. These results identify hemolytic red blood cells and iron as novel players in the tumor microenvironment that repolarize TAMs to exert direct anti-tumor effector function. Thus, the delivery of iron to TAMs emerges as a simple adjuvant therapeutic strategy to promote anti-cancer immune responses.