Nanoparticle-Loaded Hydrogel Patches on Cells for Drug Delivery

Cell surface patches provides a potential approach to deliver therapeutics to targeted tissues. The goal of this work is to form a drug-loaded patch on the surface of cells without altering the capacity for cell-substrate interactions on non-coated regions. Our approach is to synthesize polymer patches on cell surface via PEG-diacrylate (PEGDA) photopolymerization and photomask-mediated photolithography. These PEGDA patches are formed using an eosin/tertiary amine initiation system with 530 nm light. The fundamental limits of feature size is probed through experimental analysis of pattern geometry, system geometry, prepolymer composition, and prepolymer viscosity. The patterning was initially studied on a glass microarray where the reaction environment is carefully controlled, and <10 micrometer features are easily attained. PEGDA polymer formation showed that high intensity, short time illumination had the best chance to accurately generate the desired PEGDA pattern. Additionally, this reaction/diffusion system was modeled using coupled differential equations in Matlab. Trends in the experimental system are directly mapped to the experimental system, and the model is used to guide the experimental approach for patterning on cells, where high intensity light is not feasible for cell function.

To demonstrate cell surface labeling, A549 cell surfaces were loaded with eosin (initiator) through sulfo-NHS coupling or through antibody interactions. Sub-10 micrometer nanoparticle-loaded patches are successfully deposited on cells, and factors promoting cell viability and function are discussed. The release of doxorubicin from nanoparticles incorporated into these coatings is quantified through doxorubicin fluorescence. The release profile is not influenced by the coating thickness, and the kinetics of release in PBS are consistent with that of the free nanoparticles in solution.