Nanomaterial Interactions with Human Neutrophils.

Neutrophils are the most abundant circulating leukocyte and the first point of contact between many drug delivery formulations and human cells. Despite their prevalence and implication in a range of immune functions, little is known about how human neutrophils respond to synthetic particulates. Here, we describe how ex vivo human neutrophils respond to particles which vary in both size (5 nm to 2 µm) and chemistry (lipids, poly(styrene), poly(lactic-co-glycolic acid), and gold). In particular, we show that (i) particle uptake is rapid, typically plateauing within 15 min; (ii) for a given particle chemistry, neutrophils preferentially take up larger particles at the nanoscale, up to 200 nm in size; (iii) uptake of nanoscale poly(styrene) and liposomal particles at concentrations of up to 5 µg/mL does not enhance apoptosis, activation, or cell death; (iv) particle-laden neutrophils retain the ability to degranulate normally in response to chemical stimulation; and (v) ingested particles reside in intracellular compartments that are retained during activation and degranulation. Aside from the implications for design of intravenously delivered particulate formulations in general, we expect these observations to be of particular use for targeting nanoparticles to circulating neutrophils, their clearance site (bone marrow), or distal sites of active inflammation.

Molecular Rotors for Universal Quantitation of Nanoscale Hydrophobic Interfaces in Microplate Format.

Hydrophobic self-assembly pairs diverse chemical precursors and simple formulation processes to access a vast array of functional colloids. Exploration of this design space, however, is stymied by lack of broadly general, high-throughput colloid characterization tools. Here, we show that a narrow structural subset of fluorescent, zwitterionic molecular rotors, dialkylaminostilbazolium sulfonates [DASS] with intermediate-length alkyl tails, fills this major analytical void by quantitatively sensing hydrophobic interfaces in microplate format. DASS dyes supersede existing interfacial probes by avoiding off-target fluorogenic interactions and dye aggregation while preserving hydrophobic partitioning strength. To illustrate the generality of this approach, we demonstrate (i) a microplate-based technique for measuring mass concentration of small (20-200 nm), dilute (submicrogram sensitivity) drug delivery nanoparticles; (ii) elimination of particle size, surfactant chemistry, and throughput constraints on quantifying the complex surfactant/metal oxide adsorption isotherms critical for environmental remediation and enhanced oil recovery; and (iii) more reliable self-assembly onset quantitation for chemically and structurally distinct amphiphiles. These methods could streamline the development of nanotechnologies for a broad range of applications.

Universal process-inert encoding architecture for polymer microparticles.

Polymer microparticles with unique, decodable identities are versatile information carriers with a small footprint. Widespread incorporation into industrial processes, however, is limited by a trade-off between encoding density, scalability and decoding robustness in diverse physicochemical environments. Here, we report an encoding strategy that combines spatial patterning with rare-earth upconversion nanocrystals, single-wavelength near-infrared excitation and portable CCD (charge-coupled device)-based decoding to distinguish particles synthesized by means of flow lithography. This architecture exhibits large, exponentially scalable encoding capacities (>10(6) particles), an ultralow decoding false-alarm rate (<10(-9)), the ability to manipulate particles by applying magnetic fields, and pronounced insensitivity to both particle chemistry and harsh processing conditions. We demonstrate quantitative agreement between observed and predicted decoding for a range of practical applications with orthogonal requirements, including covert multiparticle barcoding of pharmaceutical packaging (refractive-index matching), multiplexed microRNA detection (biocompatibility) and embedded labelling of high-temperature-cast objects (temperature resistance).