Surface-Initiated Polymerization within Mesoporous Silica Spheres for the Modular Design of Charge-Neutral Polymer Particles

We report a templating approach for the preparation of functional polymer replica particles via surface-initiated polymerization in mesoporous silica templates. Subsequent removal of the template resulted in discrete polymer particles. Furthermore, redox-responsive replica particles could be engineered to disassemble in a reducing environment. Particles, made of poly­(methacryloyloxyethyl phosphorylcholine) (PMPC) or poly­[oligo­(ethylene glycol) methyl ether methacrylate] (POEGMA), exhibited very low association to human cancer cells (below 5%), which renders the reported charge-neutral polymer particles a modular and versatile class of highly functional carriers with potential applications in drug delivery

Fluidized Bed Layer-by-Layer Microcapsule Formation

Polymer microcapsules can be used as bioreactors and artificial cells; however, preparation methods for cell-like microcapsules are typically time-consuming, low yielding, and/or involve custom microfluidics. Here, we introduce a rapid (∼30 min per batch, eight layers), scalable (up to 500 mg of templates), and efficient (98% yield) microcapsule preparation technique utilizing a fluidized bed for the layer-by-layer (LbL) assembly of polymers, and we investigate the parameters that govern the formation of robust capsules. Fluidization in water was possible for particles of comparable diameter to mammalian cells (>5 μm), with the experimental flow rates necessary for fluidization matching well with the theoretical values. Important variables for polymer film deposition and capsule formation were the concentration of polymer solution and the molecular weight of the polymer, while the volume of the polymer solution had a negligible impact. In combination, increasing the polymer molecular weight and polymer solution concentration resulted in improved film deposition and the formation of robust microcapsules. The resultant polymer microcapsules had a thickness of ∼5.5 nm per bilayer, which is in close agreement with conventionally prepared (quiescent (nonflow) adsorption/centrifugation/wash) LbL capsules. The technique reported herein provides a new way to rapidly generate microcapsules (approximately 8 times quicker than the conventional means), while being also amenable to scale-up and mass production

A Framework to Account for Sedimentation and Diffusion in Particle–Cell Interactions

In vitro experiments provide a solid basis for understanding the interactions between particles and biological systems. An important confounding variable for these studies is the difference between the amount of particles administered and that which reaches the surface of cells. Here, we engineer a hydrogel-based nanoparticle system and combine in situ characterization techniques, 3D-printed cell cultures, and computational modeling to evaluate and study particle–cell interactions of advanced particle systems. The framework presented demonstrates how sedimentation and diffusion can explain differences in particle–cell association, and provides a means to account for these effects. Finally, using in silico modeling, we predict the proportion of particles that reaches the cell surface using common experimental conditions for a wide range of inorganic and organic micro- and nanoparticles. This work can assist in the understanding and control of sedimentation and diffusion when investigating cellular interactions of engineered particles

Ligand-Functionalized Poly(ethylene glycol) Particles for Tumor Targeting and Intracellular Uptake

Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly­(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g–1) when compared with the PEG (3% ID g–1) and PEG-RDG (7% ID g–1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems

Ligand-Functionalized Poly(ethylene glycol) Particles for Tumor Targeting and Intracellular Uptake

Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly­(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g–1) when compared with the PEG (3% ID g–1) and PEG-RDG (7% ID g–1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems