Biomimetic particles as therapeutics

Abstract

In recent years, there have been major advances in the development of novel nanoparticle- and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health.

Keywords: biomaterial; biomimetic; drug delivery; micro/nanoparticle.

Figure 1

Particle shape is a critical factor in antigen presenting cell biomimicry. (a) T-Cell (red) interacts with the long axis of an ellipsoidal artificial antigen presenting cell (green). Widefield view of (b,d) spherical and (c,e) ellipsoidal aAPC interacting with (b,c) cognate and (d,e) non-cognate T-Cells. (f) Ellipsoidal aAPC leads to greater frequency of conjugates between T-Cells and aAPC compared to spherical aAPC. (g) Ellipsoidal aAPC leads to greater length of contact between T-Cell and aAPC compared to spherical aAPC. (h) Nanoellipsoidal aAPC leads to greater in vivo proliferation and activation of T-Cells compared to equivalent spherical aAPC. Modified reproduction with permission from Sunshine et al, Biomaterials (2014) [45] and Meyer et al, Small (2014) [46].

Figure 2

Paracrine release of IL-2 by a targeted nanoparticle therapeutic enhances T-Cell proliferation and activation. (a) Schematic illustration of experimental conditions to test the efficacy of paracrine delivery of IL-2. In the transwell condition, the particle and cells are separated by a transwell barrier. In the uncoated condition, the particle and cells are mixed together but there is no targeted delivery of the IL2. (b) The highest T-Cell fold expansion is observed in the groups with targeted paracrine delivery of IL-2 by artificial antigen presenting cell particles. (c) CD-25 (IL-2 receptor) expression is highest in the group with targeted paracrine delivery of IL-2. (d) Computational modeling of local juxtapositional concentration effects. With the narrowing of the gap between the aAPC and the cell, there is an increase in the available local concentration of the released therapeutic. Reproduced with permission from Steenblock et al, J Biol Chem (2011) [70].

Figure 3

Schematics of (A) bottom-up, fully synthetic, biomimetic particle supported lipid bilayers, reprinted with permission from Ashley et al., Nat Mater. (2011)[93] and (B) top-down particle coating with biological membranes, reprinted with permission from Hu et al., PNAS (2011)[97].

Figure 3

Schematics of (A) bottom-up, fully synthetic, biomimetic particle supported lipid bilayers, reprinted with permission from Ashley et al., Nat Mater. (2011)[93] and (B) top-down particle coating with biological membranes, reprinted with permission from Hu et al., PNAS (2011)[97].