Understanding the Biomolecular Corona Formation at the Nano-Bio Interface: Toward the Development of Immune Evasive Nanoparticles

• Applicant: Dr. Alessia Besford
• Subject Area: Polymer Materials ; Biological and Biomimetic Chemistry ; Biomaterials
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451339898

Engineered hydrogel nanoparticles are promising candidates for application in controlled and targeted therapeutic drug delivery. A key challenge in this pursuit is overcoming the rapid clearance of administered particles from the blood stream, which is triggered by the rapid deposition of biomolecules on the nanoparticles’ surface from the extracellular fluid. During this deposition process, the biomolecular corona is formed, which can lead to undesired recognition and ultimately internalization of the nanoparticles by phagocytes, and the activation of complement and coagulation cascades. Implementing stealth (avoidance of cellular recognition and internalization) and low-fouling (protein resistance) properties to the nanoparticles, is commonly and broadly achieved through functionalization with hydrophilic and charge-neutral polymers such as polyethylene glycol (PEG). In my proposed project, I challenge this traditional approach to “shield” nanoparticles from immune recognition using stealth and low-fouling technologies, and propose a shift towards exploiting immunomodulatory biomolecules on the nanomaterial structure that are capable of inhibiting immune-mediated destruction (i.e. to work with immune system components, not against it). Specifically, I propose to synthesize PEG-based nanoparticles using surface initiated-atom transfer radical polymerization, and subsequently incorporate heparin into the nanoparticle structure for its anticoagulant properties and to bind bioactive molecules such as factor H, antithrombin III, CD47, and CD55. These molecules will actively counteract immunoreactions or mark the particles as "self", thereby reducing immune responses. State of the art human whole blood assays that uniquely identify specific cell uptake of nanoparticles, along with hemocompatibility tests will be performed to comprehensively assess and understand interactions with the multiple components of the immune system. This will be linked to in-depth proteomics characterization data of the biomolecular corona. Decoding the immunological "meaning" of the biomolecular corona, and establishing an immunogenic link towards nanoparticle clearance, will further assist in understanding the possibilities of immune evasion of nanoparticles. This may ultimately be employed in the development of advanced long circulating nanoparticle systems for the controlled delivery of drugs for the therapeutic treatment of disease.

• DFG Programme: Research Grants