Modulation of Chloroquine in nanoparticle uptake: a review

The application of nanotechnology in several areas of medicine has been promising, however, there are still serious problems, such as in the area of oncology, for example. Although nanoparticles can accumulate 10 times more in tumors, less than 1% of the injected dose actually reaches the tumor, as they are retained mainly in the liver and spleen. Liver-specific macrophages, called Kupffer cells, are one of the main barriers to the use of nanoparticles for cancer treatment. These Kupffer Cells are part of the Mononuclear Phagocytic System (MPS) and exhibit endocytic activity against materials that pass through the blood and enter the liver. For this reason, Kupffer cells are central to the process of eliminating nanoparticles that cross the body's epithelial barriers. Still, chloroquine can act directly on the MPS, helping the nanoparticles reach their final target. This review addresses the main studies with chloroquine acting in the MPS, which could revolutionize cancer treatment or other biological applications.

Pathology and Pathogenesis of Lassa Fever: Novel Immunohistochemical Findings in Fatal Cases and Clinico-pathologic Correlation

Background Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the “at risk” seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of three million, and fatalities up to 67,000, demonstrating the serious impact of the disease on the region and global health. Methods Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. Results Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. Conclusions The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of LF is multifactorial and additional studies are needed.

Nanoparticles to Target and Treat Macrophages: The Ockham’s Concept?

Nanoparticles are nanomaterials with three external nanoscale dimensions and an average size ranging from 1 to 1000 nm. Nanoparticles have gained notoriety in technological advances due to their tunable physical, chemical, and biological characteristics. However, the administration of functionalized nanoparticles to living beings is still challenging due to the rapid detection and blood and tissue clearance by the mononuclear phagocytic system. The major exponent of this system is the macrophage. Regardless the nanomaterial composition, macrophages can detect and incorporate foreign bodies by phagocytosis. Therefore, the simplest explanation is that any injected nanoparticle will be probably taken up by macrophages. This explains, in part, the natural accumulation of most nanoparticles in the spleen, lymph nodes, and liver (the main organs of the mononuclear phagocytic system). For this reason, recent investigations are devoted to design nanoparticles for specific macrophage targeting in diseased tissues. The aim of this review is to describe current strategies for the design of nanoparticles to target macrophages and to modulate their immunological function involved in different diseases with special emphasis on chronic inflammation, tissue regeneration, and cancer.

Proteo-transcriptomic profiling of nasal mononuclear phagocytic system cells in human controlled allergen challenge

Immune homeostasis is essential to protect mucosal airway surfaces from unnecessary and damaging inflammation against inhaled harmless environmental antigens, such as allergens. However, in allergic individuals this protective homeostatic response seems absent. Innate cells part of the mononuclear phagocytic system (MPS) play an important role in these processes. Most of our knowledge on allergic immune responses comes from animal models or from peripheral blood immune responses. Information on human tissue-specific responses is scarce, however allergen-specific immune responses are initiated locally and this information is crucial for the development of novel therapies. Here we performed mass-cytometry proteomics and single cell RNA sequencing on immune cells from nasal biopsies of allergic rhinitis subjects and healthy controls, before and three days after repeated nasal challenge with House Dust Mite allergen. Following challenge, patients displayed an increased clinical score together with enhanced eosinophilia, a cardinal feature of allergic inflammation. Although clinically silent, we observed a distinct, local, innate immune response to allergen in healthy individuals, characterized by infiltration of HLA-DRlow CD14+ monocytes expressing anti-microbial genes (S100A8, S100A9, S100A12) as well as transcriptional activation in cDC2, including several tolerogenic genes (NR4A1, IL4I1, TIMP1). The innate response in allergic individuals indicated an inflammatory role for infiltrating HLA-DRhi CD14+ monocytes, CD16+ monocytes, and CD1A+ cDC2 (ALOX15, CD1A, CCL17), in the development/maintenance of an allergic response. Future therapies should be addressing those innate MPS populations, either enhancing or reducing their activity for the treatment of inflammatory airway disease.