Complement: Alive and Kicking Nanomedicines

Andersen, Alina Joukainen; Hashemi, Sayed Hossein; Andresen, Thomas Lars; Hunter, A. Christy; Moghimi, S. Moein

doi:10.1166/jbn.2009.1045

Cited by 65 publications

(53 citation statements)

References 48 publications

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“…23,24 Here, we showed that IONPs provoked complement activation resulting in the generation of the anaphylatoxins C3a and C5a as well as the soluble terminal complement complex sC5b-9 in an ex vivo human whole blood model. Moreover, the IONPs induced the secretion of pro-inflammatory cytokines in whole blood from healthy donors.…”

Section: Discussionmentioning

confidence: 88%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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Iron oxide nanoparticles (IONPs) are promising nanomaterials for biomedical applications. However, their inflammatory potential has not been fully established. Here, we used a lepirudin anti-coagulated human whole blood model to evaluate the potential of 10 nm IONPs to activate the complement system and induce cytokine production. Reactive oxygen species and cell death were also assessed. The IONPs activated complement, as measured by C3a, C5a and sC5b-9, and induced the production of pro-inflammatory cytokines in a particle-dose dependent manner, with the strongest response at 10 µg/mL IONPs. Complement inhibitors at C3 (compstatin analog Cp40) and C5 (eculizumab) levels completely inhibited complement activation and secretion of inflammatory mediators induced by the IONPs. Additionally, blockade of complement receptors C3aR and C5aR1 significantly reduced the levels of various cytokines, indicating that the particle-induced secretion of inflammatory mediators is mainly C5a and C3a mediated. The IONPs did not induce cell death or reactive oxygen species, which further suggests that complement activation alone was responsible for most of the particle-induced cytokines. These data suggest that the lepirudin anti-coagulated human whole blood model is a valuable ex vivo system to study the inflammatory potential of IONPs. We conclude that IONPs induce complement-mediated cytokine secretion in human whole blood.

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Section: Discussionmentioning

confidence: 88%

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Wolf-Grosse¹,

Rokstad²,

Ali³

et al. 2017

IJN

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“…11,64,83 Mechanistically this is due to the generation of the terminal part of the complement pathway where the membrane attack complex is generated (C5b-9). This forms holes in biomembranes; in the case of bacteria this results in destruction of the cell by osmosis.…”

Section: Complement Activationmentioning

confidence: 99%

Smart polymers in drug delivery: a biological perspective

Hunter

Moghimi

2017

Polym. Chem.

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Key to the widespread application of smart polymers in drug delivery is understanding the mechanistic interplay, as well as consequence, of the presence of these macromolecules within living systems. This review looks at these interactions in terms of host response to macromolecular structure and subsequent clinical implications. In order to highlight this, three distinct routes of drug delivery are discussed, enabling a journey from the outside of the body in to the cell. This is used to contrast the need for different scientific approaches replete to successful drug delivery in these physiologically diverse areas. The discussion initiates with the application of smart polymers to the oral route of drug delivery, followed by macromolecular fate within the systemic circulation and finally intracellular delivery. The advantages, in terms of biological performance, as well as the challenges of using smart polymers within this multifaceted arena are delineated.

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“…This makes its assembly and deposition on to the surface of a nanomaterial with high surface area (e.g. nanofibres, nanoparticles) rather difficult [6]. Furthermore, a surface-bound C3b is expected to occupy an area of 40 nm2 [7].…”

Section: Contact Angle Measurementsmentioning

confidence: 99%

IN-VITRO IMMUNOCOMPATIBILITY & CHARACTERIZATION AT NANOSCALE OF THIN FILMS AND VASCULAR MEDICAL DEVICES.

Janjic¹,

Kavatzikidou²,

Karagkiozaki³

et al. 2017

IJAR

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Texture.Immunocompatibility comprises a complex response which depends both on the physico-chemical characteristics of the biomaterial and on the hereditary and acquired ability of the recipient to react. Objective: The objective of the present work was the comparative study of the immunocompatibility of different materials and their morphological characterization. Methods: The three types of thin films used in this work were the titanium nitride [TiN],Titanium [Ti] and the amorphous hydrogenated diamond-like carbon [a-C:H], which are deposited onto a silicon substrate by Magnetron Sputtering and Plasma-Enhanced Chemical Vapor Deposition (PECVD), respectively. Medical devices used in this study, were the silicon coated Latex irrigation catheter and the endoprosthesis such as vascular grafts [Dacron, PTFE] and stent grafts [Nitinol stent graft, Cobalt Chromium stent graft]. Bare silicon substrate and serum were used as a "negative" control and the Latex [elastomer-elastic hydrocarbon polymer] as a "positive" control. Complement C5 convertase [C5c] activation was assessed using the sandwich enzyme immunoassay-sandwich ELISA for the specific time periods [0min, 15 min, 30 min and 60 min] at wavelength of 450nm. The morphological characterization of the materials was conducted by Scanning Electron Microscopy (SEM). The study of biomaterials topography was conducted by Atomic Force Microscopy (AFM) and their surface wettability properties by Contact Angle measurements. Results: Our results show that both groups of materials (the nanomaterials and the medical devices) are not likely to cause any immunological adverse reaction and as a result might be characterized and selected as excellent candidates for medical applications. Conclusions: The effectiveness of the study is attributed to the measurement of a single factor in serum in order to acquire important information about the materials' properties e.g immunological response. The possibility to modify the above tested parameters during

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Complement: Alive and Kicking Nanomedicines

Cited by 65 publications

References 48 publications

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Iron oxide nanoparticles induce cytokine secretion in a complement-dependent manner in a human whole blood model

Smart polymers in drug delivery: a biological perspective

IN-VITRO IMMUNOCOMPATIBILITY & CHARACTERIZATION AT NANOSCALE OF THIN FILMS AND VASCULAR MEDICAL DEVICES.

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