Modularity of RBC hitchhiking with polymeric nanoparticles: testing the limits of non-covalent adsorption

Vincent Lenders; Remei Escudero; Xanthippi Koutsoumpou; Laura Armengol Álvarez; Jef Rozenski; Stefaan J Soenen; Zongmin Zhao; Samir Mitragotri; Pieter Baatsen; Karel Allegaert; Jaan Toelen; Bella B Manshian

doi:10.1186/s12951-022-01544-0

Modularity of RBC hitchhiking with polymeric nanoparticles: testing the limits of non-covalent adsorption

J Nanobiotechnology. 2022 Jul 16;20(1):333. doi: 10.1186/s12951-022-01544-0.

Authors

Vincent Lenders¹, Remei Escudero¹, Xanthippi Koutsoumpou¹, Laura Armengol Álvarez², Jef Rozenski², Stefaan J Soenen^{1

3}, Zongmin Zhao^{4

5}, Samir Mitragotri^{6

7}, Pieter Baatsen^{8

9}, Karel Allegaert^{10

11

12

13}, Jaan Toelen^{12

13

14}, Bella B Manshian^{15

16}

Affiliations

¹ Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Herestraat 49, B3000, Louvain, Belgium.
² Medicinal Chemistry, Rega Institute for Medical Research, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B3000, Louvain, Belgium.
³ NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Herestraat 49, B3000, Louvain, Belgium.
⁴ Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, 60612, USA.
⁵ University of Illinois Cancer Center, Chicago, IL, 60612, USA.
⁶ John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA02138, USA.
⁷ Wyss Institute of Biologically Inspired Engineering, Harvard University, Boston, MA02115, USA.
⁸ VIB-KU Leuven Center for Brain and Disease Research Electron Microscopy Platform of the VIB Bioimaging Core, Louvain, Belgium.
⁹ Department of Neurosciences, Leuven Brain Institute, KU Leuven, B3000, Louvain, Belgium.
¹⁰ Department of Hospital Pharmacy, Erasmus MC University Medical Center, 3015, CN, Rotterdam, the Netherlands.
¹¹ Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B3000, Louvain, Belgium.
¹² Leuven Child and Youth Institute, KU Leuven, 3000, Leuven, Belgium.
¹³ Woman and Child, Department of Development and Regeneration, KU Leuven, 3000, Louvain, Belgium.
¹⁴ Department of Pediatrics, University Hospitals Leuven, 3000, Louvain, Belgium.
¹⁵ Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, Herestraat 49, B3000, Louvain, Belgium. bella.manshian@kuleuven.be.
¹⁶ NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Herestraat 49, B3000, Louvain, Belgium. bella.manshian@kuleuven.be.

Abstract

Red blood cell (RBC) hitchhiking has great potential in enhancing drug therapy, by improving targeting and reducing rapid clearance of nanoparticles (NPs). However, to improve the potential for clinical translation of RBC hitchhiking, a more thorough understanding of the RBC-NP interface is needed. Here, we evaluate the effects of NP surface parameters on the success and biocompatibility of NP adsorption to extracted RBCs from various species. Major differences in RBC characteristics between rabbit, mouse and human were proven to significantly impact NP adsorption outcomes. Additionally, the effects of NP design parameters, including NP hydrophobicity, zeta potential, surfactant concentration and drug encapsulation, on RBC hitchhiking are investigated. Our studies demonstrate the importance of electrostatic interactions in balancing NP adsorption success and biocompatibility. We further investigated the effect of varying the anti-coagulant used for blood storage. The results presented here offer new insights into the parameters that impact NP adsorption on RBCs that will assist researchers in experimental design choices for using RBC hitchhiking as drug delivery strategy.

Keywords: Drug delivery; Non-covalent adsorption; Polymeric nanoparticles; Red blood cells; Surface properties.

MeSH terms

Adsorption
Animals
Drug Delivery Systems / methods
Erythrocytes
Humans
Mice
Nanoparticles* / therapeutic use
Polymers / pharmacology
Rabbits

Substances

Polymers