Engineered Nanoparticles for Drug Delivery in Cancer Therapy *
Valerio Voliani in Nanomaterials and Neoplasms, 2021
When nanoparticles enter the plasma, opsonization (i.e., the adsorption of serum proteins) will occur immediately on their surfaces [5, 160a]. Through opsonization, foreign organisms or particles will be coated with nonspecific proteins known as opsonins to generate a corona and make the particles more visible to the phagocytic cells in the MPS. Opsonins typically contain complement proteins and immunoglobins (usually IgG) along with albumins, fibronectins, fibrinogens, and apolipoproteins [194]. Studies have shown that the corona has a layered architecture. It starts with an inner layer of proteins that strongly adsorb onto the surface, with Kd 10−6 to 10−8 m, to form the hard corona, which is then surrounded by a layer of soft corona formed by weak interactions [169, 195]. The primary driving forces for opsonization are based on hydrophobic and electrostatic interactions, together with entropic and conformational changes for the adsorbed proteins [196]. Depending on the charge and hydrophobicity of the nanoparticles, opsonization can occur within minutes. Experimental results suggest that a charged surface tends to be covered by proteins more rapidly than their counterparts with a neutral surface [160a].
Inherited Defects in Immune Defenses Leading to Pulmonary Disease
Stephen D. Litwin in Genetic Determinants of Pulmonary Disease, 2020
Phagocytes, including alveolar macrophages, circulating monocytes, and PMN leukocytes, possess bactericidal mechanisms. Interaction between microbes, opsonizing humeral factors, and the phagocytic surface membrane results in phagocytosis. The term opsonin includes specific antibacterial antibodies, complement components, and other cofactors. As would be expected, hypogammaglobulinemia and complement deficiencies seriously impair the opsonizing capacity of serum. Opsonized bacteria are ingested within a phagocytic vacuole and then killed intracellularly. The microbicidal mechanism involves an increase in oxygen consumption and glucose consumption by the phagocytic cell, and participation of the hexose monophosphate shunt. Mechanisms of phagocytosis and bacterial killing are covered in other monographs of this series.
The immune and lymphatic systems, infection and sepsis
Peate Ian, Dutton Helen in Acute Nursing Care, 2020
Antibodies or immunoglobulins have a number of functions and effects: On activation, they bind to the pathogen, causing clumping or agglutination.Once bound, they act as opsonins, identifying or signalling that particular antigen for phagocytosis.Binding triggers the production of identical plasma cells or clones, which all produce the same antibody; this is called clonal expansion.Phagocytosis and the complement cascade system are also activated.
Transferrin decorated PLGA encumbered moxifloxacin nanoparticles and in vitro cellular studies
Published in Drug Development and Industrial Pharmacy, 2023
Gayathri Aparnasai Reddy, Mayank Handa, Debapriya Garabadu, Ravindra Kumar, Pramod Kumar Kushawaha, Rahul Shukla
Polymeric NPs like PLGA, polycaprolactone, and poly lactic acid, when administered via the intravenous (IV) route, are rapidly uptake by the mononuclear phagocytic system (MPS). Furthermore, opsonin attachment on the surface of the NPs results in recognition by phagocytosis. It results in the elimination of NPs from the body due to the reticuloendothelial system (RES) when administered IV [16,19]. Hence, to prevent the rapid uptake by RES, PEGylation helps the NPs to escape from the RES system. Masking with PEG provides hydrophobicity to polymeric NPs by its adsorption on the surface of NPs. Moreover, delivering the drugs to the targeted site is desirable rather than the nonselective delivery of these cargos [20]. However, size of NPs plays a prominent role in RES uptake and inhibition. The size below 200 nm bypasses the RES and inhibits the need of PEGylation. To impart targeting to NPs, effective coating with ligands can be done.
Role of Mac-1 integrin in generation of extracellular vesicles with antibacterial capacity from neutrophilic granulocytes
Published in Journal of Extracellular Vesicles, 2020
Ákos M. Lőrincz, Balázs Bartos, Dávid Szombath, Viktória Szeifert, Csaba I. Timár, Lilla Turiák, László Drahos, Ágnes Kittel, Dániel S. Veres, Ferenc Kolonics, Attila Mócsai, Erzsébet Ligeti
To test the involvement of the two opsonin receptor types separately and independently from phagocytosis, we used relevant adhesive surfaces. Participation of Fc receptors in EV formation was investigated on immune complex surface but we did not observe significant increase of EV generation as compared to the control where Fc receptors are not activated (Figure 2(b)). In parallel experiments, we verified that neutrophils adherent to the immune complex surface were able to produce superoxide (Figure S3o), indicating that activation of the Fc receptors did take place and the lack of EV production increase was not the result of missing cell activation. Next we examined the potential role of complement receptors. On neutrophils the dominant complement receptors are CR3 and CR4, which belong to the family of β2 integrins and can be specifically activated by the complement fragment C3bi [44]. As shown in Figure 2(c), adding human PMN on a C3bi surface resulted in a significant increase in the number of detectable EVs. Thus, activation of the complement receptors is effective in EV biogenesis also in the absence of phagocytosis.
Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide
Published in Journal of Drug Targeting, 2018
Liping Zhang, Yanan Shi, Yina Song, Dongyu Duan, Xuemei Zhang, Kaoxiang Sun, Youxin Li
After NPs enter the circulation, they are adsorbed by plasma opsonins. The latter can adsorb foreign substances and accelerate the phagocytosis of these substances via the reticuloendothelial system (RES). The most important opsonins are complement and immunoglobulins. The RES can recognise opsonins specifically. Hence, most NPs adsorbed onto opsonins are recognised by the RES and are ‘swallowed up’ by phagocytic cells to reach the target organ. Targeted protein modification can selectively guide NPs to the target organ, reduce the phagocytosis of NPs by the RES, and prolong the circulation time in vivo. In our study, Dir-labelled Tf-NPs uptake by the liver and spleen was reduced, and prolongation in the circulation of Tf-NPs was obvious. Biodistribution studies revealed Dir-labelled NPs to be distributed in the heart, liver, spleen, lungs, kidneys, stomach and intestine after oral administration for 6 h, whereas Dir-labelled Tf-NPs were distributed mainly in the small intestine. Tfs targeted the small intestine; the TfR reduced NPs phagocytosis by the RES and prolonged the circulation time in the body.
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