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Rational Design of Polymeric Nanoconstructs for Drug Delivery and Biomedical Imaging
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Anna Lisa Palange, Miguel Ferreira, Daniele Di Mascolo, Roberto Palomba, Pietro Lenarda, Alexander Cook, Paolo Decuzzi
As with any other systemically administered nanoparticles, DPNs are also subjected to mononuclear phagocyte system (MPS) uptake. Following nanoparticle intravascular administration, one of the major issues to overcome is the rapid clearance from the blood circulation by resident macrophages of the liver, spleen, and lungs. These cells continuously monitor the blood environment for pathogens and debris to be removed. Administered nanoparticles are recognized by these cells as foreign objects to be removed from the blood circulation [66]. This process entraps nanoparticles in these organs, impacting the number of nanoparticles effectively reaching the target site. The main organ implied in this process is the liver with the Kupffer cells. Kupffer cells represent the 80–90% of the tissue macrophages present in the body. These cells are continuously exposed to the blood flow since they reside within the lumen of the liver sinusoid. Another important organ for nanoparticle removal from the blood flow is the spleen. Here, the same activity is performed by the splenic marginal zone macrophages and the red pulp macrophages which are crucial for the trapping of blood-borne particulate antigens and for the clearance of opsonized cells, respectively. Finally, the lungs are also involved in the clearance of particulates from the blood stream. This action is mainly conducted by the pulmonary intravascular macrophages, which, in some species, exert similar activity to that of Kupffer cells [67–70].
Immune System Imaging
Published in Margarida M. Barroso, Xavier Intes, In Vivo, 2020
Michael J. Hickey, M. Ursula Norman
The spleen is the body’s largest secondary lymphoid organ, containing approximately one-fourth of the body’s lymphocytes. Its primary functions are two-fold: 1) surveying the blood for foreign material/infectious agents and mounting immune responses to captured foreign antigens, and 2) removal of old or defective red blood cells (RBCs) from circulation. These functions are carried out in morphologically distinct compartments termed the white pulp (immune regulation) and the red pulp (filtering of aging RBCs), with these regions being separated by an interface called the marginal zone (MZ) (Figure 18.4). Different leukocyte populations in these compartments are specialized to carry out specific functions. For example, the red pulp consists of a network of reticular fibers interspersed with macrophages specialized in phagocytosis and recycling components of defective RBCs, while in the MZ, different populations of macrophages are specialized in removal of blood-borne pathogens. This section will highlight how imaging techniques have advanced our understanding of leukocyte behavior within different compartments of the spleen under steady-state conditions and during immune responses.
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Kim M. Tsoi, Sonya A. Macparland, Xue-Zhong Ma, Vinzent N. Spetzler, Juan Echeverri, Ben Ouyang, Saleh M. Fadel, Edward A. Sykes, Nicolas Goldaracena, Johann M. Kaths, John B. Conneely, Benjamin A. Alman, Markus Selzner, Mario A. Ostrowski, Oyedele A. Adeyi, Anton Zilman, Ian D. Mcgilvray, Warren C. W. Chan
Finally, we asked whether flow dynamics and microarchitecture could be used to predict nanomaterial uptake in the spleen. We found that nanomaterial accumulation reflects blood velocity, as almost all nanomaterials were found within the red pulp region (see Fig. 17.4a). Washout studies have demonstrated that blood preferentially slows down in the red pulp, where it has a half-life of ∼10 min (Refs. 39,40). Like the hepatic sinusoid, the red pulp is rich in macrophages. As macrophages in the hepatic sinusoid and the splenic red pulp are exposed to nanomaterial-containing blood flowing at a very slow rate, we hypothesized that quantum dot uptake would be comparable between the two macrophage types. However, when we analysed quantum dot uptake in splenic mononuclear cells isolated from quantum-dot-treated rats, we found that splenic macrophages took up significantly less nanomaterial than Kupffer cells. 12 h post-injection, only 25.4 ± 10.1% of splenic macrophages were quantum-dot-positive, compared to 84.8 ± 6.4% of Kupffer cells (see Fig. 17.4b,c). Splenic macrophages also took up ten times less nanomaterial on a per cell basis (see Fig. 17.4b,c). A similar trend was seen 4 h post-injection (see Fig. 17.4c). This suggests that cellular phenotype within the MPS also contributes to uptake. Despite similar opportunity, splenic macrophages have less endocytic/phagocytic affinity for nanomaterials than their counterparts in the liver. We confirmed the role of cellular phenotype by comparing quantum dot uptake by primary splenic and hepatic macrophages in vitro. As anticipated, Kupffer cells took up more quantum dots than did splenic macrophages (see Fig. 17.4d,e). At the 80 nM dose, 59.9 ± 9.0% of Kupffer cells were quantum-dot-positive, compared to 35.1 ± 10.4% of splenic macrophages and the MFI for Kupffer cells was approximately double that for splenic macrophages. The same trend was found for other nanomaterial designs. Interestingly, the liver–spleen difference is more pronounced in vivo, and this may relate to other anatomical and physiological differences between the organs. First, despite their location in the “slow flow” red pulp region of the spleen, splenic macrophages may not have the same access to transiting nanomaterials as do Kupffer cells in the liver. Second, the rat liver receives approximately 21% of the cardiac output via both the hepatic artery and the portal vein, whereas the spleen receives only 1% via the splenic artery18,41.
Histological analysis of the effects of cadmium, chromium and mercury alone and in combination on the spleen of male Sprague-Dawley rats
Published in Journal of Environmental Science and Health, Part A, 2020
Chantelle Venter, Anel Olivier, Helena Taute, Hester M. Oberholzer
In the red pulp areas of the spleen, macrophages form an integral part of the immune system and its main function is to locate foreign bodies, engulf and then digest them through the process of phagocytosis.[10] In the spleen it mainly engulfs old and/or damaged red blood cells. No cellular alterations were observed in the red pulp region of the control group (Fig. 1A). The Cd exposed group (Fig. 1C) showed minimal depletion of cells in the red pulp region, this is similar to previous literature in which some necrosis was seen as a result of Cd toxicity in the spleen by Dumkova and co-authors in 2016.[12] The Cr exposed group (Fig. 1E) revealed a moderate depletion of cells in the red pulp region, this occurrence is similar to what was observed during a previous study performed by Das Neves,Santos,de Pereira and de Jesus.[13] It was concluded that Cr toxicity led to the depletion of red pulp cells which is directly related to the process of phagocytosis. The Hg exposed group (Fig. 1G) revealed severe depletion of cells in the red pulp region. Mercury has a high bio-accumulation within the spleen, specifically the red pulp region which may lead to an increase of apoptosis of cells being constantly exposed to this metal.[14] All the combination groups revealed severe depletion in the cells located in the red pulp region. The severity of the cellular alterations in the Cd and Cr combination group (Fig. 2I) may be attributed to an additive effect when administered in combination. Although no studies have been done on the spleen and simultaneous metal exposure, other studies have been done on the effects of heavy metals alone and in combination on the liver and kidney tissue and coagulation system. Some alterations to tissues and cells were found and thus the alterations to the spleen tissue seen in the present study is expected.[15,16]