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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.
Nano-Biomedicine: A Next-Generation Tool for Effective and Safe Therapy
Published in Rajesh Singh Tomar, Anurag Jyoti, Shuchi Kaushik, Nanobiotechnology, 2020
Vikas Shrivastava, Pallavi Singh Chauhan, Rajesh Singh Tomar
Blood vessels and arteries are known to be the natural routes for the delivery of various nutrients, removal of toxic materials, and drug delivery [36]. But the controlled and specific access to various specific tissues and organs is somewhere lacking. The role of NPs is thus providing access to cells, tissues, and organs. Intravenous delivery provides rapid circulation followed by filtration using Kupffer cells and the marginal zone and red pulp [37]. The size and NPs surface play an essential role in the opsonization of blood and clearance as the bulk particles (200 nm and above) are more susceptible to efficiently activate the human complement system as compared to the NPs [38]. Surface property of NPs like types of functional groups; affect the binding process of blood proteins to opsonins.
PEGylated liposomes: immunological responses
Published in Science and Technology of Advanced Materials, 2019
Marwa Mohamed, Amr S. Abu Lila, Taro Shimizu, Eman Alaaeldin, Amal Hussein, Hatem A. Sarhan, Janos Szebeni, Tatsuhiro Ishida
There appears to be a strong inverse relationship between the extent of the ABC phenomenon and the phospholipid dose for the initial dose of PEGylated liposomes, regardless of liposomal phospholipid composition. The higher the lipid dose, the lower the ABC phenomenon [57,58]. We speculate that low concentrations of phospholipid could activate marginal zone B cells (MZ-B), and trigger anti-PEG IgM production, while higher initial doses of PEGylated liposomes could cause MZ-B to elicit immunological tolerance or anergy [59,60]. MZ-B cells are a specialized population of B cells that are located in the marginal zone of the spleen. They secrete antibodies that help to protect against blood-borne viruses and bacteria. Rats injected intravenously with doses higher than 5 μmol phospholipid/kg did not exhibit increased levels of anti-PEG IgM and the subsequent ABC phenomenon. On the other hand, the ABC phenomenon was significantly increased at phospholipid doses less than 1 μmol phospholipid/kg [58,61,62]. Such difference also might be due to difference in the pharmacokinetics of PEGylated liposomes and/or reactivity of MZ-B with PEGylated liposomes in different species as described above.
Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: a review
Published in Science and Technology of Advanced Materials, 2019
Kouichi Shiraishi, Masayuki Yokoyama
Researchers have identified the involvement of complement activation in PEG-related immune responses, regarding which Dams et al. suggested some serum factors [38–40]. The complement activation facilitates uptake of PEG-liposomes in phagocytic cells [40]. These results indicate that PEG-liposomes induce anti-PEG IgM responses during the first administration. IgM antibodies are unable to directly facilitate phagocytic uptake owing to the absence of Fc receptors for IgM-mediated phagocytic uptake [41]. However, anti-PEG IgM antibody-bound complexes involve complements, which—in classic pathways during the second administration—facilitate phagocytic uptake by complement receptors on such phagocytic cells as hepatic Kupffer cells, splenic marginal zone and red-pulp macrophages, and blood monocytes [39,42]. Therefore, serum complements are significantly involved in the ABC phenomenon. Although these results have been observed in PEG-liposome cases, and although the roles of complement systems in other PEG-NPs remain unclear, complement systems will likely play an important role in other PEG-NPs. In fact, most nanoparticles have been known to activate complements by either themselves or through serum proteins to some extent. Not only activation of complements, certain complement activation pathways promote anti-inflammatory M2-phenotype macrophages, which further promote tumor growth [43,44]. These suggest possibilities of correlation between nanoparticles, host’s immune system, and tumor tissues. These relations are beyond the scope of this review, however, we must bear in mind that any kind of particles affect host immune systems. Above-mentioned studies have suggested possible roles of anti-PEG Abs, serum factors, and phagocytic activities, all of which are responsible for the rapid clearance phenomenon. So far, several studies have examined various PEGylated or novel hydrophilic polymer-based nanoparticle systems regarding the rapid-clearance phenomenon as it occurs over the course of multiple administrations, and have compared mainly those nanoparticle systems with PEG-liposomes [45–48]. In fact, PEG-liposomes have been used as a positive control for the ABC phenomenon. In other words, PEG-liposomes are the most efficient PEG-NPs to exhibit the ABC phenomenon, and researchers have compared PEG-NPs with PEG-liposomes. It should be mentioned that anti-PEG IgM is necessary for observation of the ABC phenomenon, but does not always ensure the complete absence of nanoparticles in blood (the ABC phenomenon). Previously, we made important findings about the ABC phenomenon. Although PEG-b-poly(β-benzyl-L-aspartate) block copolymer micelles (PEG-PBLA micelles) induced anti-PEG IgM, the ABC phenomenon was not observable in PEG-PBLA micelles [49]. This observation is critical to clarifying the ABC phenomenon, which is an integral part of PEG-related humoral immune responses. We will describe this function later in the review. The important point to bear in mind here is that the potency of PEG-NP immunogenicity is a more important issue than the observability or the non-observability of the ABC phenomenon.