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Cell-bound Nanoparticles for Tissue Targeting and Immunotherapy: Engineering of the Particle-Membran

Nanoparticles have been developed as vehicles for delivering a variety of payloads including small molecules, nucleic acids and proteins. To overcome the non-specific biodistribution of nanomaterials and target specific sites in vivo, there has been a surge of interest in using autologous cells as nanoparticle carriers. In order to design cell-nanoparticle constructs for active targeting, an understanding of the physicochemical interactions that underline nanoparticle adhesion, detachment, and uptake is necessary. In this review, we critically analyze the various properties that affect cell-nanomaterial interactions. We describe how physical properties of the cellular plasma membrane such as curvature, membrane tension and lipid composition affect the attachment of nanoparticles. We discuss the effect of nanoparticle properties including size, shape, stiffness, and chemical composition as well as the environmental conditions on the cell-nanoparticle interactions. We conclude with an overview of recent applications of cell-nanoparticle constructs including cellular hitchhiking, backpacking and responsive surface attachment for drug delivery1.


(a) Surfaces on a scale of mm-cm induce cellular spreading and attachment. Adapted from [57] Copyright (2018) National Academy of Sciences b) Particles on the scale of ∼10 um induce membrane deformation and spreading for attachment. Copyright (2020) Wyss Institute at Harvard university. Particle interaction varies with transition from (c) nanoscale surface adhesion to (d) complete internalization of micron sized particles. (c) adapted with permission from [10] licensed under CC 4.0. (d) adapted with permission from [58] Copyright (2012) Wiley.
Cell-nanoparticle interactions vary with length scale

Cell-nanomaterial interactions rely on the energetics of membrane deformation by nanoparticle adsorption, and the dependence of such energetics on the physical properties of the plasma membrane. Particle properties also influence the favorability of membrane adhesion and probability of forming a stable bound state. The environmental conditions during the attachment such as agitation, temperature and relative concentrations of nanoparticles and cells also influence the cell-nanoparticle interactions. Since particle uptake by cells is triggered when a partially membrane-wrapped state transitions to a fully wrapped state, understanding the factors that control membrane adhesion and wrapping is critical to maintaining the nanoparticles on the exterior of the cell.



1.https://www.sciencedirect.com/science/article/pii/S1359029420301151#fig3

Supriya Prakash, Ninad Kumbhojkar, John R. Clegg, Samir Mitragotri,

Cell-bound Nanoparticles for Tissue Targeting and Immunotherapy: Engineering of the Particle-Membrane Interface,

Current Opinion in Colloid & Interface Science,

2020,

101408,

ISSN 1359-0294,

https://doi.org/10.1016/j.cocis.2020.101408.