Characterisation of Polymeric Nanoparticle-Protein Interactions

Daramy, K. (Speaker)
Perrie, Y. (Speaker)
Caterina Minelli (Contributor)
Rattray, Z. (Speaker)

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Activity: Talk or presentation types › Oral presentation

Description

(W4125V) Characterisation of Polymeric Nanoparticle-Protein Interactions

Period	20 Oct 2021
Held at	American Association of Pharmaceutical Scientists, United States
Degree of Recognition	International

Keywords

Polymeric
Nanoparticles
Protein

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Purpose: Nanomedicine is the application of nanotechnology for clinical applications such as diagnosis and treatment of disease. Nanomedicine is a rapidly growing field which shows significant potential for the development of new medicines for unmet clinical need. As of 2019 over 50 nanomedicines were approved by the FDA and the EMA for clinical use. Upon being administered to a biological system, nanoparticles interact with biomolecules and circulating proteins which spontaneously adsorb onto the nanoparticle surface to form the ‘protein corona’. The formation of the protein corona alters the physiochemical properties (shape, charge, size) of nanoparticles which will subsequently alter its biological identity and biological fate. Protein corona formation changes the biological properties of nanoparticles which is exemplified by changes in the site of in vivo nanoparticle accumulation, altered rates of nanoparticle cellular uptake and changes in the drug release profiles of nanoparticles. The combined impact of these factors may lead to changes in nanoparticle biodistribution and the safety and efficacy of a drug product. Therefore, the aim of this study is to develop a robust and reproducible pipeline for the characterisation of nanoparticle-protein interactions that can be implemented for the development of safer and more effective nanomedicines. Methods: Here, we report the investigation of nanoparticle-protein interactions for Latex Polystyrene and poly(lactic-co-glycolic acid) (PLGA) model nanoparticles. Briefly, nanoparticle samples were incubated in 10% v/v Foetal Bovine Serum (FBS) at various timepoints (2 and 24 hours) and at 37°C using gentle agitation to mimic physiological conditions. Changes in nanoparticle physical and chemical properties (particle size, concentration and charge) were measured using Dynamic Light Scattering (DLS), Resonant Mass Measurement (RMM) and Nanoparticle Tracking Analysis (NTA) alongside parallel analyses of protein composition with SDS-PAGE. Results: The data obtained support the use of RMM for the analysis of the impact of protein corona formation and colloidal behaviour of PLGA nanoparticles. The results show that at early incubation timepoints (i.e. 2 hours), the changes are caused by nanoparticle-protein interactions which lead to an increase in particle size due to protein corona formation while at later timepoints (i.e. 24 hours) the changes correspond to nanoparticle-nanoparticle-protein interactions which lead to nanoparticle agglomeration (up to 10-fold increase relative to control). Overall, introducing PLGA and PLGA-PEG model nanoparticles to protein containing media resulted in the emergence of particle sub-populations of varying size. Conclusion: It is well known that nanoparticle recovery techniques (e.g. centrifugation-wash) can lead to changes in the protein corona composition. Therefore, it is important to develop new tools that can compare in situ protein corona formation with that of the ex situ protein corona for nanoparticles recovered from protein-containing incubation media. An advantage of using RMM is that recovery of the nanoparticles from the incubation medium is not required, and that these measurements were performed while mimicking cell culture conditions. This approach enables the non-invasive assessment of changes occurring in nanoparticle size when introduced to a biological system. References: Capriotti, A.L. et al. (2014) 'Analytical Methods for Characterizing the Nanoparticle–Protein Corona'. Chromatographia, 77 (11), pp. 755-769. Nguyen, V.H. and Lee, B.J. (2017) 'Protein corona: a new approach for nanomedicine design'. Int J Nanomedicine, 12 3137-3151. Rampado, R. et al. (2020) 'Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of "Stealthy" Nanomaterials'. Front Bioeng Biotechnol, 8 166. Acknowledgement: The authors acknowledge the Strathclyde EPSRC Doctoral Training Programme for funding this PhD scholarship.

Characterisation of Polymeric Nanoparticle-Protein Interactions

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Characterization of polymeric nanoparticle-protein interactions

Characterization of polymeric nanoparticle-protein interactions