Complement activation by gold nanoparticles passivated with polyelectrolyte ligands

Abstract

We reported that the surface area and hydrophilicity of polyelectrolyte-coated gold nanoparticles influence their complement activation, a biological response not well understood to date.

Immunotoxicity Considerations for Next Generation Cancer Nanomedicines

“…Moreover, this group also looked at the effect of various shapes (spherical and rod‐shaped), coatings (different charges and hydrophilicities) and sizes (spherical diameter of 20 and 40 nm; cylindrical diameter of 40 nm and length of 10 nm) of GNP on complement activation. The larger the surface area and greater the positive charge was found to be the biggest inducers of complement activation in this case …”

“…CARPA is one of the most significant immunotoxicity challenges for cancer nanomedicines in the pipeline, contributing to the clinical withdrawal of a host of IONP and resulting in the release of safety reports for both liposomal and iron oxide nanoformulations by EMA. Recent papers have been published, however, which go into great depth on the influence of different nanoparticle shapes, surface areas, coatings and charges on complement activation, and offer suggestions to alleviating this activity . Furthermore, although the molecular events leading to CARPA are yet to be fully established, the mechanisms involved are becoming a lot clearer, with the importance of the formed protein corona on nanomaterials (Section ) and its interaction with immunoglobulins now understood as a significant event leading to complement activation .…”

Synthetic Glyconanoparticles Modulate Innate Immunity but Not the Complement System

“…Although sometimes beneficial in prophylactic protection, uncontrolled complement activation is harmful and contributes to disease progression . In cancer therapeutics, complement activation by nanoparticles has several implications and gold nanoparticles are also known to interact with the complement system. − To be used as an immunotherapeutic these glyconanoparticles must not induce complement-mediated anaphylaxis. Thus, we sought to study the effect of the mannosylated glycogold nanoparticles of the complement system.…”

Immunomodulatory properties of nanostructured systems for cancer therapy

“…111 Ensuring the control of the complement responses triggered by the amino and hydroxyl groups present on the nanocomposite surface is a major challenge. 112 When NPs are subjected to conjugation with polymers, different structural conformations may produce distinct complement responses, even for the same surface composition. 109,113 For example, the use of NPs with a diameter of 250 nm conjugated with dextran helped activate the complement cascade, while similar results were not observed for the same NPs with a diameter of 600 nm, indicating the influence of NP size on the recruited response.…”