Zernike Seminar - Olga Koshkina - Tailor-Made Nanocarriers: from the Bench to Clinic

Personalized therapies with theranostic nanocarriers promise to solve major public health problems. Equipped with a therapeutic and diagnostic function, these nanocarriers transport the therapeutics precisely to the site of disease and provide imaging contrast for diagnostics. Yet, no theranostic nanocarrier has reached the clinical use. My overall goal is to develop efficient polymeric nanocarriers for imaging and therapy. To achieve this goal, it is crucial to produce functional nanoparticles, understand their physicochemical properties, and to correlate them to function. In my presentation, I am going to address several aspects that are important for the development of nanocarriers, including:

1) Surface functionalization of nanoparticles. I will focus on the modification with the thermoresponsive poly(2-oxazolines) that enables control of the interactions between nanoparticles and serum using temperature as a stimulus. 1

2) Development of nanoparticles loaded with perfluorocarbons for multimodal imaging with 19F Magnetic Resonance Imaging and ultrasound.2,3 Here, I will show, how polymeric nanoparticles that display an unusual fractal structure can overcome several challenges, including the long organ retention.

3) Scaling up the production of nanoparticles for clinical use with microfluidics.4

4) Production of anisotropic supraparticles via the evaporation-driven assembly of colloidal building blocks.5

Overall, my talk will cover several stages in the development of functional nanoparticles from the bench to clinic, highlighting the physicochemical aspects that govern the function of nanocarriers.

1. Koshkina O.; Lang, T.; Docter, D.; Stauber, R.; Secker S.; Schlaad H.; Weidner, S. Mohr B.; Maskos M.‡,*; Bertin A.‡, Temperature-Triggered Protein Adsorption on Polymer-Coated Nanoparticles in Serum, Langmuir, 2015, 31, 8873–8881.

2. Koshkina, O. ‡; Lajoinie, G. ‡; Baldelli, F.; Swider, E.; Cruz, J. L.; White, P.; Schweins, R.; Dolen, Y.; van Dinther, E.; Voets, I. K.; Rogers, S. E.; van Eck, E.R.H.; Heerschap, A.; Versluis, M.; de Korte, C.; Figdor, C. G.; de Vries, I. J. *; Srinivas M‡,*., Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking, Adv. Funct. Mater., 2019, 19, 1806485.

3. Koshkina, O.*; White, P.B. ‡; Staal. A.H.J. ‡; Schweins, R. ‡; Swider, E.; Tirotta, I.; Tinnemans, P.; Fokkink, R.; Veltien, A.; van Riessen, N. K.; van Eck, E.R.H.; Heerschap, A., Metrangolo, P.; Baldelli Bombelli, F.*; Srinivas, M.*, Nanoparticles for “Two Color” 19F Magnetic Resonance Imaging: Towards Combined Imaging of Biodistribution and Degradation, J. Colloid Interface Sci., 2020, 565, 278-287.

4. Hoogendijk, E.; Swider, E.; Staal, A.H.J.; White, P.B.; van Riessen, N.K.; Glaßer, G.; Lieberwirth, I.; Musyanovych, A.; Serra, C.A.; Srinivas, M. ‡,*; Koshkina, O. ‡,*, Continuous-flow Production of Perfluorocarbon-loaded Polymeric Nanoparticles: from the Bench to Clinic, ACS Appl. Mater. Interfaces., 2020, doi.org/10.1021/acsami.0c12020.

5. Raju, L.T. ‡; Koshkina, O.‡; Tan, H.; Riedinger, A.; Landfester, K.*; Lohse, D.; Zhang, X.*, Particles Size Determines the Shape of Supraparticles Formed in Evaporating Ternary Droplets, ACS Nano, accepted.