Advances in the development of engineered nanoparticles (NPs) have resulted in several nanopharmaceuticals for clinical use.
However, the therapeutic index of these nanoparticles depends on their fate in the body and their interaction with the biological medium. On intravenous administration, the NPs are confronted with components of the innate immune system, especially the complement system. Complement is an enzymatic humoral pattern-recognition defence system that helps in eliminating pathogens or any foreign material circulating in the blood. Once in the blood, NPs trigger uncontrolled complement activation leading to opsonisation by complement protein C3 and rapid clearance through phagocytosis by macrophages eventually resulting in decreased therapeutic activity of NPs.
Additionally, nanoparticle ingestion by macrophages also contributes to the infusion-related reactions or life-threatening hypersensitivity reactions. Therefore, an improved understanding of mechanisms that lead to the clearance and toxicities of these NPs will not just help in accelerating the growth of the nanomedicine sector but also sets a path for personalised therapies. With this main goal, ESR 4 in the DIRNANO project aims to deeply study the nanoparticle’s interaction with the body’s defence lines. The key element of the project is to develop refined nano engineering strategies needed to design NPs that escape detection by the complement system.
To do so, ESR 4 will explore new strategies for NPs surface functionalisation through polymer pairing approach and grafting of complement inhibitors to overcome complement activation and adverse proinflammatory responses by macrophages.
This study will help in the development of innovative complement benign surfaces for targeted drug delivery along with the improved understanding of interactive forces controlling nanomaterials and innate immune system.
Hajira Banu Haroon - Early Stage Researcher
School of Pharmacy - Newcastle University (UK)