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Magnetic Nanoparticles: Challenges and Opportunities in Drug Delivery
Published in Jeffrey N. Anker, O. Thompson Mefford, Biomedical Applications of Magnetic Particles, 2020
Allan E. David, Mahaveer S. Bhojani, Adam J. Cole
In many cases, MNPs rely on the circulatory system (i.e. blood flow) in order to reach the target tissue. Nanoparticles, and indeed any other substance introduced into the body, have several possible fates; they may: (1) enter the blood circulation, (2) distribute into body tissues, (3) be degraded, or (4) be excreted from the body. This is often termed ADME, for absorption, distribution, metabolism, and excretion. The rate and extent to which each of these processes occurs determines the pharmacokinetics of the particle. Pharmacokinetics, a quantitative description of how a substance travels through the body, how the body acts upon it, and how it is eliminated from the body, are therefore an important consideration for design of MNP-based drug delivery systems. Surface properties and size of the MNP have the greatest impact on the particle’s pharmacokinetics (Yoo, Chambers, and Mitragotri 2010). These properties determine the extent of MNP interaction with the mononuclear phagocyte system (MPS), which is a part of the immune system comprised of a group of cells whose primary function is to eliminate foreign particles from the body. Note that in some texts, the MPS is referred to as the “reticuloendothelial system (RES),” but this is an older term that is no longer in favor as it gives incorrect prominence to endothelial cells, which do not play a major role in this process.
Radionuclide Labeling and Imaging of Magnetic Nanoparticles
Published in Nguyễn T. K. Thanh, Clinical Applications of Magnetic Nanoparticles, 2018
Benjamin P. Burke, Christopher Cawthorne, Stephen J. Archibald
The fate of MNPs when systemically administered is governed by their absorption, distribution, metabolism and excretion (ADME). A range of factors have a significant impact on these pharmacokinetic parameters and thus the ultimate biodistribution of the NPs, including size, shape, coating, charge and interaction with plasma proteins. An understanding of how these parameters interact is central to the rational design of agents for both tumour targeting and toxicity. The major clearance route for MNPs is the mononuclear phagocytic system (MPS),2 consisting of blood-borne monocytes as well as the various tissue-resident macrophage populations that derive from them.3 NP interactions with macrophages are mediated in the same way as extracellular pathogens, i.e. facilitated by opsonization and recognition,4 and the rate of degradation of MNPs after phagocytosis is largely unknown.
Exosomes in Cancer Disease, Progression, and Drug Resistance
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Taraka Sai Pavan Grandhi, Rajeshwar Nitiyanandan, Kaushal Rege
Dendritic cells, monocytes, and macrophages constitute the mononuclear phagocyte system which are largely responsible for constantly surveying the body for any signs of external or internal disease. These white blood cells, responsible for engulfing foreign substances and cellular debris, identify diseased and infected cells based on the surface expression of proteins that distinguish them from healthy counterparts. Upon internalization and digestion of the diseased cell proteins, these cells have the ability to present the antigen to the naïve T-cells initiating an immune response. Cancer cells evade immune detection by creating a microenvironment that allows their progression and metastases, and exosomes play an important role in the development of an immune-suppressive microenvironment. Salimu et al. [66] showed that DU145 prostate cancer cell-derived exosomes immunosuppress dendritic cells by inducing the expression of CD73 protein, which results in the inhibition of proinflammatory cytokines TNFα and IL12 production. Exosomal prostaglandin E2 (PGE2) was found as the potential driver of CD73 induction and subsequent inhibition of TNFα and IL12 production. Immunosuppressed dendritic cells were unable to elicit an immune response as measured by the impaired CD8+ T cell responses. Cancer cell-derived exosomal PGE2 was also shown to impact differentiation of myeloid cells in the bone marrow. Xiang et al. [67]. showed that murine breast carcinoma-derived exosomes are taken up by myeloid cells in the bone marrow which induce their differentiation towards immunosuppressive myeloid-derived suppressor cell (MDSCs) phenotype. The authors showed that the PGE2 and TGF-β in the exosomes were responsible for the accumulation of the (CD11b+ Gr-1+) MDSCs. Addition of anti-PGE2 and anti-TGFβ antibodies significantly reduced the accumulation of (CD11b+ Gr-1+) MDSC cells. Immunosuppressive MDSCs have been implicated in recruiting CD4+ Foxp3+ CD25+ regulatory T cells that create an immunosuppressive environment in the tumor by actively suppressing the proliferation of CD4+ and CD8+ T cells [68].
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
Nanocarriers with certain physical and chemical characteristics, in some circumstances in animal experiments, have been reported to prime the host-immune system, resulting in severe adverse effects and/or lack of therapeutic efficacy of the encapsulated drug [10–12]. For instance, surface electrostatic charges and/or particle size of developed nanocarriers are fundamental to define such immune responses [13]. In these experiments, the nanoparticles are essentially recognized as foreign particles by immune cells, which induce multilevel immune responses. In addition, the nanoparticles have been reported to interact with circulating serum proteins, such as complement proteins belonging to the primary humoral immune system, resulting in their rapid systemic clearance by the cells of mononuclear phagocyte system (MPS) [14,15]. Mononuclear phagocyte system (MPS), composed of dendritic cells (DCs), monocytes and macrophages, is a part of the innate immune system that plays a critical role in phagocytosis of pathogen and foreign substances in all phases of the immune response. Taken together, these interactions with the immune system have the potential to influence the in vivo fate of administrated nanocarriers and might impair their therapeutic performance.