He, Jiajin; (2025) Towards the Control of Nanoparticle - Protein Corona Interactions. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Despite the significant potential of nanomedicine for cancer drug delivery, the development of products in this field remains limited. This limitation is partly due to the formation of the protein corona around nanoparticles. The protein corona can modify the pharmacokinetics and biodistribution of nanoparticles, potentially resulting in accelerated clearance from the body and triggering immune responses, which impedes effective tumour targeting. As such, a comprehensive understanding and control of protein corona formation—particularly the outer 'soft corona,' which is critical but underexplored—are essential for advancing nanomedicine applications. Most research has focused on the 'hard corona' (firmly bound proteins). However, the 'soft corona,' composed of proteins that are weakly adsorbed, plays a crucial role in determining the biological fate of nanoparticles. In the present study, a Protein Corona Capture Depletion Method was developed for analysing corona dynamics, particularly the soft corona. This method could enable systematic modulation of the corona, optimising nanoparticles for improved cancer cell uptake and enhanced immune evasion. The role of surface charge in corona formation was also examined using polystyrene nanoparticles with different charges (NH2-PSNP, COOH-PSNP).

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