Obtaining nonspherical poly(alkylcyanoacrylate) nanoparticles by the stretching method applied with a marketed water-soluble film

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.

Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy.

Vascular endothelium offers a variety of therapeutic targets for the treatment of cancer, cardiovascular diseases, inflammation, and oxidative stress. Significant research has been focused on developing agents to target the endothelium in diseased tissues. This includes identification of antibodies against adhesion molecules and neovascular expression markers or peptides discovered using phage display. Such targeting molecules also have been used to deliver nanoparticles to the endothelium of the diseased tissue. Here we report, based on in vitro and in vivo studies, that the specificity of endothelial targeting can be enhanced further by engineering the shape of ligand-displaying nanoparticles. In vitro studies performed using microfluidic systems that mimic the vasculature (synthetic microvascular networks) showed that rod-shaped nanoparticles exhibit higher specific and lower nonspecific accumulation under flow at the target compared with their spherical counterparts. Mathematical modeling of particle-surface interactions suggests that the higher avidity and specificity of nanorods originate from the balance of polyvalent interactions that favor adhesion and entropic losses as well as shear-induced detachment that reduce binding. In vivo experiments in mice confirmed that shape-induced enhancement of vascular targeting is also observed under physiological conditions in lungs and brain for nanoparticles displaying anti-intracellular adhesion molecule 1 and anti-transferrin receptor antibodies.