Studying the interactions between nanoengineered materials and biological systems plays a vital role in the development of biological applications of nanotechnology and the improvement of our fundamental understanding of the bio-nano interface. A significant barrier to progress in this multidisciplinary area is the variability of published literature with regards to characterizations performed and experimental details reported. Here, we suggest a 'minimum information standard' for experimental literature investigating bio-nano interactions. This standard consists of specific components to be reported, divided into three categories: material characterization, biological characterization and details of experimental protocols. Our intention is for these proposed standards to improve reproducibility, increase quantitative comparisons of bio-nano materials, and facilitate meta analyses and in silico modelling.

The use of natural compounds for preparing hybrid molecular films-such as surface coatings made from metal-phenolic networks (MPNs)-is of interest in areas ranging from catalysis and separations to biomedicine. However, to date, the film growth of MPNs has been observed to proceed in discrete steps (≈10 nm per step) where the coordination-driven interfacial assembly ceases beyond a finite time (≈1 min). Here, it is demonstrated that the assembly process for MPNs can be modulated from discrete to continuous by utilizing solid-state reactants (i.e., rusted iron objects). Gallic acid etches iron from rust and produces chelate complexes in solution that continuously assemble at the interface of solid substrates dispersed in the system. The result is stable, continuous growth of MPN films. The presented double dynamic process-that is, etching and self-assembly-provides new insights into the chemistry of MPN assembly while enabling control over the MPN film thickness by simply varying the reaction time.

Materials assembled by coordination interactions between naturally abundant polyphenols and metals are of interest for a wide range of applications, including crystallization, catalysis, and drug delivery. Such an interest has led to the development of thin films with tunable, dynamic properties, however, creating bulk materials remains a challenge. Reported here is a class of metallogels formed by direct gelation between inexpensive, naturally abundant tannic acid and group(IV) metal ions. The metallogels exhibit diverse properties, including self-healing and transparency, and can be doped with various materials by in situ co-gelation. The robustness and flexibility, combined with the ease, low cost, and scalability of the coordination-driven assembly process make these metallogels potential candidates for chemical, biomedical, and environmental applications.

Nanoengineered materials offer tremendous promise for developing the next generation of therapeutics. We are transitioning from simple research questions, such as "can this particle eradicate cancer cells?" to more sophisticated ones like "can we design a particle to preferentially deliver cargo to a specific cancer cell type?" These developments are poised to usher in a new era of nanoengineered drug delivery systems. We primarily work with templating methods for engineering polymer particles and investigate their biological interactions. Templates are scaffolds that facilitate the formation of particles with well-controlled size, shape, structure, stiffness, stability, and surface chemistry. In the past decade, breakthroughs in engineering new templates, combined with advances in coating techniques, including layer-by-layer (LbL) assembly, surface polymerization, and metal-phenolic network (MPN) coordination chemistry, have enabled particles with specific physicochemical properties to be engineered. While materials science offers an ever-growing number of new synthesis techniques, a central challenge of therapeutic delivery has become understanding how nanoengineered materials interact with biological systems. Increased collaboration between chemists, biologists, and clinicians has resulted in a vast research output on bio-nano interactions. Our understanding of cell-particle interactions has grown considerably, but conventional in vitro experimentation provides limited information, and understanding how to bridge the in vitro/in vivo gap is a continuing challenge. As has been demonstrated in other fields, there is now a growing interest in applying computational approaches to advance this area. A considerable knowledge base is now emerging, and with it comes new and exciting opportunities that are already being capitalized on through the translation of materials into the clinic. In this Account, we outline our perspectives gained from a decade of work at the interface between polymer particle engineering and bio-nano interactions. We divide our research into three areas: (i) biotrafficking, including cellular association, intracellular transport, and biodistribution; (ii) biodegradation and how to achieve controlled, responsive release of therapeutics; and (iii) applications, including drug delivery, controlling immunostimulatory responses, biosensing, and microreactors. There are common challenges in these areas for groups developing nanoengineered therapeutics. A key "lesson-learned" has been the considerable challenge of staying informed about the developments relevant to this field. There are a number of reasons for this, most notably the interdisciplinary nature of the work, the large numbers of researchers and research outputs, and the limited standardization in technique nomenclature. Additionally, a large body of work is being generated with limited central archiving, other than vast general databases. To help address these points, we have created a web-based tool to organize our past, present, and fut...

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Upon exposure to human blood, nanoengineered particles interact with a multitude of plasma components, resulting in the formation of a biomolecular corona. This corona modulates downstream biological responses, including recognition by and association with human immune cells. Considerable research effort has been directed toward the design of materials that can demonstrate a low affinity for various proteins (low-fouling materials) and materials that can exhibit low association with human immune cells (stealth materials). An implicit assumption common to bio–nano research is that nanoengineered particles that are low-fouling will also exhibit stealth. Herein, we investigated the link between the low-fouling properties of a particle and its propensity for stealth in whole human blood. High-fouling mesoporous silica (MS) particles and low-fouling zwitterionic poly­(2-methacryloyloxyethyl phosphorylcholine) (PMPC) particles were synthesized, and their interaction with blood components was assessed before and after precoating with serum albumin, immunoglobulin G, or complement protein C1q. We performed an in-depth proteomics characterization of the biomolecular corona that both identifies specific proteins and measures their relative abundance. This was compared with observations from a whole blood association assay that identified with which cell type each particle system associates. PMPC-based particles displayed reduced association both with cells and with serum proteins compared with MS-based particles. Furthermore, the enrichment of specific proteins within the biomolecular corona was found to correlate with association with specific cell types. This study demonstrates how the low-fouling properties of a material are indicative of its stealth with respect to immune cell association.

The nanoengineering of particles is of interest for both fundamental and applied science. How particles are made substantially affects their properties and quality, and therefore usefulness. Disseminating current understanding of particle engineering can help facilitate the use of existing technologies, as well as guide future developments. Herein, we describe three methods used in our laboratory for the nanoengineering of particles, based on templated assembly, and discuss important considerations for each. Firstly, we describe the use of layer-by-layer assembly for depositing multilayered nanofilms on particle surfaces to generate core-shell particles and hollow capsules. Secondly, we detail the use of mesoporous silica templating for the engineering of porous polymer replica particles. Thirdly, we describe how the coordination of phenolic compounds and metal ions can be used to fabricate thin films via metal-phenolic network formation on particle templates. We provide stepwise, easy-to-follow guides for each method, and discuss commonly encountered challenges and obstacles, with considerations for how to alter these protocols to achieve desired particle properties. While we intend for these guides to be easily accessible to researchers new to particle engineering, we believe they can also provide useful insight to all researchers working in the field of engineering advanced particles.

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.