Unusual nanoparticles for multiscale imaging in personalised medicine: From bench to bedside

Wednesday. August 25, 2021

Mangala Srinivas

Wageningen University and Research and Cenya Imaging BV

Abstract

We have developed a nanoparticle-based imaging platform1 that allows imaging using 19F MRI2, PET (in submission), SPECT3, ultrasound4, photoacoustics5, fluorescence, and EM (unpublished). We are working on these nanoparticles to label and image therapeutic cells, such as dendritic cells or engineered T cells in vivo, in a longitudinal and quantitative manner. This information is vital to the optimisation of cell therapy in oncology and regenerative medicine.

The nanoparticles consist of a polymer-entrapped perfluorocarbon of about 200 nm in diameter. Here, I will discuss what we have learned about the internal structure of the nanoparticles, where the super-hydrophobic perfluorocarbon appears hydrated, and how this unusual structure impacts its biological properties. Importantly, the unusual multi-core structure of the nanoparticles has biological impact; we found that the 200 nm particles break down into smaller domains where the perfluorocarbon remains stabilized and results in 15x faster clearance in vivo, compared to core-shell particles6.

The nanoparticles are approved for a clinical trial tracking therapeutic dendritic cells in the Netherlands. We are also working on upscaling technology7 at GMP grade.

References:

1. Srinivas, M. et al. Customizable, multi-functional fluorocarbon nanoparticles for quantitative in vivo imaging using 19F MRI and optical imaging. Biomaterials 31, 7070–7077 (2010).

2. Srinivas, M. et al. PLGA-encapsulated perfluorocarbon nanoparticles for simultaneous visualization of distinct cell populations by 19F MRI. Nanomedicine (Lond). 10, 2339–48 (2015).

3. M, K. et al. Characterization of Intrinsically Radiolabeled Poly(lactic- co-glycolic acid) Nanoparticles for ex Vivo Autologous Cell Labeling and in Vivo Tracking. Bioconjug. Chem. (2021) doi:10.1021/ACS.BIOCONJCHEM.1C00271.

4. Koshkina, O. et al. Multicore Liquid Perfluorocarbon-Loaded Multimodal Nanoparticles for Stable Ultrasound and 19 F MRI Applied to In Vivo Cell Tracking. Adv. Funct. Mater. 29, (2019).

5. Swider, E. et al. Clinically-applicable perfluorocarbon-loaded nanoparticles for in vivo photoacoustic,19f magnetic resonance and fluorescent imaging. Nanotheranostics 2, 258–268 (2018).

6. Staal, A. H. J. et al. In vivo clearance of 19F MRI imaging nanocarriers is strongly influenced by nanoparticle ultrastructure. Biomaterials 261, (2020).

7. Hoogendijk, E. et al. Continuous-Flow Production of Perfluorocarbon-Loaded Polymeric Nanoparticles: From the Bench to Clinic. ACS Appl. Mater. Interfaces (2020) doi:10.1021/acsami.0c12020.