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.

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.

Immobilized Particle Imaging for Quantification of Nano- and Microparticles.

The quantification of nano- and microparticles is critical for diverse applications relying on the exact knowledge of the particle concentration. Although many techniques are available for counting particles, there are some limitations in regards to counting with low-scattering materials and facile counting in harsh organic solvents. Herein, we introduce an easy and rapid particle counting technique, termed "immobilized particle imaging" (IPI), to quantify fluorescent particles with different compositions (i.

Multifunctional Thrombin-Activatable Polymer Capsules for Specific Targeting to Activated Platelets.

Smart poly(2-oxazoline) (POx)-based multifunctional polymer capsules that specifically target glycoprotein (GP) IIb/IIIa on the surface of activated platelets are degraded by the serine protease thrombin and release the urokinase plasminogen activator loaded into the polymer capsules, only in the area of acute thrombosis.

Interfacing materials science and biology for drug carrier design.

Over the last ten years, there has been considerable research interest in the development of polymeric carriers for biomedicine. Such delivery systems have the potential to significantly reduce side effects and increase the bioavailability of poorly soluble therapeutics. The design of carriers has relied on harnessing specific variations in biological conditions, such as pH or redox potential, and more recently, by incorporating specific peptide cleavage sites for enzymatic hydrolysis.

Versatile Loading of Diverse Cargo into Functional Polymer Capsules.

Polymer microcapsules are of particular interest for applications including self-healing coatings, catalysis, bioreactions, sensing, and drug delivery. The primary way that polymer capsules can exhibit functionality relevant to these diverse fields is through the incorporation of functional cargo in the capsule cavity or wall. Diverse functional and therapeutic cargo can be loaded into polymer capsules with ease using polymer-stabilized calcium carbonate (CaCO) particles.

Tuning particle biodegradation through polymer-peptide blend composition.

We report the preparation of polymer-peptide blend replica particles via the mesoporous silica (MS) templated assembly of poly(ethylene glycol)-block-poly(2-diisopropylaminoethyl methacrylate-co-2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl methacrylate) (PEG45-b-P(DPA55-co-PgTEGMA4)) and poly(l-histidine) (PHis). PEG45-b-P(DPA55-co-PgTEGMA4) was synthesized by atom transfer radical polymerization (ATRP), and was coinfiltrated with PHis into poly(methacrylic acid) (PMA)-coated MS particles assembled from different peptide-to-polymer ratios (1:1, 1:5, 1:10, or 1:15). Subsequent removal of the sacrificial templates and PMA resulted in monodisperse, colloidally stable, noncovalently cross-linked polymer-peptide blend replica particles that were stabilized by a combination of hydrophobic interactions between the PDPA and the PHis, hydrogen bonding between the PEG and PHis backbone, and π-π stacking of the imidazole rings of PHis side chains at physiological pH (pH ∼ 7.

Convective polymer assembly for the deposition of nanostructures and polymer thin films on immobilized particles.

We report the preparation of polymer particles via convective polymer assembly (CPA). Convection is used to move polymer solutions and cargo through an agarose gel that contains immobilized template particles. This method both coats and washes the particles in a process that is amenable to automation, and does not depend on passive diffusion or electrical currents, thus facilitating incorporation of fragile and nanoscale objects, such as liposomes and gold nanoparticles, into the thin polymer films.

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.

Engineering enzyme-cleavable hybrid click capsules with a pH-sheddable coating for intracellular degradation.

The engineering of layer-by-layer (LbL) hybrid click capsules that are responsive to biological stimuli is reported. The capsules comprise a pH-sheddable, non cross-linked outer coating that protects enzyme-cleavable inner layers. Upon cellular uptake, the outer coating is released and the capsules are enzymatically degraded.

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.

Endocytic capsule sensors for probing cellular internalization.

A new class of polymer capsules with an in-built endocytic pH-coupled fluorescence switch is reported. These capsules display reversible "on/off" fluorescence in response to cellular pH variations. Using this system, the high-throughput quantification between surface-bound and internalized capsules is demonstrated.

Clickable Poly(2-oxazoline) Architectures for the Fabrication of Low-Fouling Polymer Capsules.

Hollow polymer capsules were prepared from linear as well as brushlike poly(2-oxazoline)s (POxs). Linear POxs containing alkene functionalities were obtained by cationic ring-opening polymerization (CROP), whereas the brush POxs bearing alkyne moieties were synthesized by a combination of CROP and reversible addition-fragmentation chain transfer (RAFT) polymerization. Multilayers consisting of POx/poly(methacrylic acid) (PMA) were sequentially deposited onto silica particle templates, and the films were stabilized either by thiol-ene (TE) chemistry or copper-catalyzed azide-alkyne cycloaddition (CuAAc).

Design of degradable click delivery systems.

Click chemistry has had a significant impact in the field of materials science over the last 10 years, as it has enabled the design of new hybrid building blocks, leading to multifunctional and responsive materials. One key application for such materials is in the biomedical field, such as gene or drug delivery. However, to meet the functional requirements of such applications, tailored degradability of these materials under biological conditions is critical.