Hydrogel Patches on Live Cells through Surface-Mediated Polymerization

Abstract

Many naturally-occurring cells possess an intrinsic ability to cross biological barriers that block conventional drug delivery, and these cells offer a possible mode of active transport across the blood brain barrier or into the core of tumor masses. While many technologies exist to form complete, nanoparticle loaded coatings on cells, a complete coating on the cell surface would disrupt the interaction of cells with their environments. To address this issue, cell surface patches that partially cover cell surfaces might provide a superior approach for cell mediated therapeutic delivery. The goal of this study is to establish a simplified approach to produce polymeric patches of arbitrary shapes on a live cell via surface-mediated photopolymerization. Cell surfaces were nonspecifically labeled with eosin, and polyethylene (glycol) diacrylate (PEGDA) coatings were directed to specific sites using a 530 nm irradiation through a chrome-coated photomask. These coatings may entrap drug loaded or imaging particles. The nonspecific formation of PEGDA hydrogel coatings increased with irradiation time, light intensity, and initiating species. 40 mW/cm2 irradiation for 5 min delivered high-resolution patterns on the surface of A549 cells, and these cells remained viable for 48 h post-patterning with fluorescent nanoparticle loaded coatings. This work first demonstrated the feasibility to photo-pattern polymer patches directly onto the surface of cells.

Coatings on mammalian cells: interfacing cells with their environment

“…However, covalent bonding generally is non-reversible [96]. Additionally, many covalent coating strategies have a significant, concentration-dependent decrease cell in viability [114].…”

“…Our lab also used a similar sulfo-NHS-biotin to covalently modify cell surfaces with biotin to later bind a streptavidin-photoinitiator conjugate. Our approach facilitated the eventual attachment of PEGDA cell patches to photoinitiator-labeled A549 cell surfaces through surface-initiated photopolymerization [114]. The PEGDA films were of thickness large enough to load nanoparticles, and sulfo-NHS-biotin concentrations in buffer below 2 mM did not impact cell viability [114].…”

“…Our approach facilitated the eventual attachment of PEGDA cell patches to photoinitiator-labeled A549 cell surfaces through surface-initiated photopolymerization [114]. The PEGDA films were of thickness large enough to load nanoparticles, and sulfo-NHS-biotin concentrations in buffer below 2 mM did not impact cell viability [114]. Covalent binding for amine group targeting has also been employed to enhance drug delivery.…”

“…PEM fabrication allows not only the formation of a complete surface coating but also the creation of polymeric cellular patches. Polymer patches are frequently designed for multiple functional cargos for a variety of potential uses including drug delivery [58, 59, 70, 114], biosensing [56, 57], and control of cell-cell communication [56]. These patches are typically fabricated through lithography on a solid substrate, adhesion of the cells to the patches, and release of the patches from the solid support.…”

Genetically Encoded Stimuli-Responsive Cytoprotective Hydrogel Capsules for Single Cells Provide Novel Genotype–Phenotype Linkage

“…Several early demonstrations of cellular encapsulation technology utilized formation of multicellular aggregates on the scale of 0.1-1 mm by relying on self-assembly of oppositely charged polyelectrolyte chains 12,13 or incorporation of cells in agarose emulsions 14 . Polymerization-based approaches have further been developed which rely on cross-linking polymer materials from monomeric precursor solutions [15][16][17][18][19][20][21] .…”