PNNL

Abstract

Nanoparticles (NPs) are emerging tools that will impact medical diagnosis and therapeutics with their capacity to specifically target cells and tissues with imaging agents and/or drug payloads.The unique physical aspects of nanoparticles present new challenges for the guidance and regulation of this promising technology. A wide variety of blood contact interactions may compromise intended nanoparticle activities and/or cause serious side effects. Activation of the complement (C) system, a powerful arm of the innate immune response, can occur on virtually any unprotected surface and severe tissue damage can accompany intense C activity. Clinical studies have indicated that doxorubicin (Doxil®) and other liposome-based nanotherapeutics, may elicit moderate to severe hypersensitivity reactions, often correlated to complement activity. ELISA-based methods used to quantify nanoparticle-dependent C activity have been limited in their sensitivity and applicability. Thus, there is an urgent need for an independent means of measuring nanoparticle-dependent complement activity. Here we describe an in vitro hemolysis-based assay of nanoparticle:complement interactions that has been developed in accordance with parallel in vivo results. It has been used to examine nanoparticles of varying size, charge and surface chemistry and could facilitate the design and assessment of next generation nanoparticles for clinical use.