Due to their ability to encapsulate both hydrophilic and hydrophobic molecules and to allow for their controlled
release, liposomes have evolved into a promising and frequently used tool in medicine, biotechnology, and bioanalysis. In this work,
we designed liposome surfaces and polymer conjugates to reliably and in a controlled fashion activate the complement system and
monitor its function. Specifically, the polymer conjugates were designed on protein, polysaccharide, or synthetic polymer backbones,
respectively, enabling flexible coupling chemistry and size tuning. They were optimized as trigger entities for efficient stimulation of
complement responses through specific surface interactions with the liposome membrane and complement proteins simultaneously.
Additionally, the liposome surface chemistry was optimized to ensure the specificity of the binding and complement stimulation.
Studies with human serum confirmed the applicability of the new assay principle providing in-depth understanding of complement
action. Specifically, increasing the density of trigger moieties enhanced the complement activation efficiency. Complement lysis
strongly relies on the physiological geometry of trigger and recognition sites and correlates with cross-linking of liposomes. Since the
liposomes demonstrated high long-term stability and the trigger entities offered a range of polymer backbones, this new principle is a
platform technology that will be applicable for a broad spectrum of assays, including immunoassays, in-depth investigations of
complement activation and regulation, and targeted release of liposome encapsulants for drug delivery systems.