Phagocytosis is a principal component of the body's innate immunity in which macrophages internalize targets in an actin-dependent manner. Targets vary widely in shape and size and include particles such as pathogens and senescent cells. Despite considerable progress in understanding this complicated process, the role of target geometry in phagocytosis has remained elusive. Previous studies on phagocytosis have been performed using spherical targets, thereby overlooking the role of particle shape. Using polystyrene particles of various sizes and shapes, we studied phagocytosis by alveolar macrophages. We report a surprising finding that particle shape, not size, plays a dominant role in phagocytosis. All shapes were capable of initiating phagocytosis in at least one orientation. However, the local particle shape, measured by tangent angles, at the point of initial contact dictates whether macrophages initiate phagocytosis or simply spread on particles. The local shape determines the complexity of the actin structure that must be created to initiate phagocytosis and allow the membrane to move over the particle. Failure to create the required actin structure results in simple spreading and not internalization. Particle size primarily impacts the completion of phagocytosis in cases where particle volume exceeds the cell volume.drug delivery ͉ macrophages ͉ membrane ͉ shape P hagocytosis is a principal component of the body's innate immunity in which macrophages and other antigenpresenting cells internalize large (Ͼ0.5 m) particulate targets (1). Examples of targets include pathogens such as rod-shaped Escherichia coli and Bacillus anthracis and spiral-shaped Campylobacter jejuni, disk-shaped senescent cells such as aged erythrocytes, and airborne particles such as dust and pollen, all of which vary widely in both shape and size. Because macrophages in the human body encounter targets with such diversity, the question has long been asked, how does target geometry impact phagocytosis? Several studies have been conducted specifically to address this question; however, a generalized answer is still lacking. The main reason behind this shortcoming is that all phagocytosis studies have been performed with spherical targets (2-7). Exclusive use of spherical particles originated partly because of a presumption that size is the principal parameter of interest and partly because of difficulties in fabricating nonspherical particles of controlled dimensions. Use of spherical particles not only concealed the role of particle shape in phagocytosis but also created an inaccurate picture of the actual role of particle size because all parameters that describe size (volume, surface area, etc.) scale with particle radius, leaving one wondering as to which parameter is of fundamental consequence in phagocytosis. Accordingly, the precise roles of target size and shape in phagocytosis, despite their high relevance, remain largely unknown.Herein, we report, using alveolar macrophages as model phagocytes and polystyrene (PS) particles o...

Nanoparticle drug delivery systems have been used in the clinic since the early 1990's. Since that time, the field of nanomedicine has evolved alongside growing technological needs to improve the delivery of various therapeutics. Over these past decades, newer generations of nanoparticles have emerged that are capable of performing additional delivery functions that can enable treatment via new therapeutic modalities. In the current clinical landscape, many of these new generation nanoparticles have reached clinical trials and have been approved for various indications. In the first issue of Bioengineering & Translational Medicine in 2016, we reviewed the history, current clinical landscape, and clinical challenges of nanoparticle delivery systems. Here, we provide a 3 year update on the current clinical landscape of nanoparticle drug delivery systems and highlight newly approved nanomedicines, provide a status update on previous clinical trials, and highlight new technologies that have recently entered the clinic.

The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies — such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs — and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.

The development of biomaterials for drug delivery, tissue engineering and medical diagnostics has traditionally been based on new chemistries. However, there is growing recognition that the physical as well as the chemical properties of materials can regulate biological responses. Here, we review this transition with regard to selected physical properties including size, shape, mechanical properties, surface texture and compartmentalization. In each case, we present examples demonstrating the significance of these properties in biology. We also discuss synthesis methods and biological applications for designer biomaterials, which offer unique physical properties.Today, biomaterials are routinely used in medical applications, such as drug delivery, tissue engineering, device-based therapies and medical imaging 1 . Many organic and inorganic materials, some of which are already available in the marketplace, have been specifically designed for promoting tissue growth and delivery of drugs. It has long been recognized that the material properties affect biological outcomes including the half-life of drugs, biocompatibility of implanted devices, and release rates and toxicity of drug carriers 2,3 . Similarly, properties of biomaterials can have a profound impact on cell proliferation and remodelling of tissues 4 . The central question that has fascinated biomedical researchers from the beginning has therefore been how to design and control material properties to achieve a specific biological response. Researchers have traditionally sought help from chemistry in answering this question. For example, release rates of drugs have been controlled through synthesis of new polymers that degrade in predictable ways 2 , and particle half-lives in the body can be prolonged by coating them with polyethylene glycol (PEG) 5 . PEG influences several other biological processes including endocytosis, protein adsorption, cell adhesion and activation of the complement system 6 . A range of biological targeting moieties, including antibodies, targeting peptides, aptamers and vitamins, have been conjugated to particles to modulate their biodistribution and to increase local therapeutic concentrations 7 . The availability of new materials has spurred the development of immunotherapies that use vaccines against diseases including certain cancers 8 and Alzheimer's disease 9 . In yet another example, short peptides derived from common extracellular matrix components, such as the Arg-Gly-Asp (RGD) tripeptide 10 , have been shown to mitigate a series of cellular functions [11][12][13] . Surface-immobilized ligands have also been discovered and used for controlling differentiation of stem cells 14,15 . Such extraordinary emphasis on chemistry is consistent with the notion that molecular recognition forms the basis of many biological functions 16 The motivation to use physical properties to control biological function comes from biology itself (Fig. 1). In nature, numerous examples can be found in which physical attributes such as shap...

We report the design of surfaces that exhibit dynamic changes in interfacial properties, such as wettability, in response to an electrical potential. The change in wetting behavior was caused by surface-confined, single-layered molecules undergoing conformational transitions between a hydrophilic and a moderately hydrophobic state. Reversible conformational transitions were confirmed at a molecular level with the use of sum-frequency generation spectroscopy and at a macroscopic level with the use of contact angle measurements. This type of surface design enables amplification of molecular-level conformational transitions to macroscopic changes in surface properties without altering the chemical identity of the surface. Such reversibly switching surfaces may open previously unknown opportunities in interfacial engineering.