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Targeted delivery of therapeutic and imaging agents in the vascular compartment represents a significant hurdle in using nanomedicine for treating hemorrhage, thrombosis, and atherosclerosis. While several types of nanoparticles have been developed to meet this goal, their utility is limited by poor circulation, limited margination, and minimal targeting. Platelets have an innate ability to marginate to the vascular wall and specifically interact with vascular injury sites. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. Inspired by this, we report the design and evaluation of nanoparticles that exhibit platelet-like functions including vascular injury site-directed margination, site-specific adhesion, and amplification of injury site-specific aggregation. Our nanoparticles mimic four key attributes of platelets, (i) discoidal morphology, (ii) mechanical flexibility, (iii) biophysically and biochemically mediated aggregation, and (iv) heteromultivalent presentation of ligands that mediate adhesion to both von Willebrand Factor and collagen, as well as specific clustering to activated platelets. Platelet-like nanoparticles (PLNs) exhibit enhanced surface-binding compared to spherical and rigid discoidal counterparts and site-selective adhesive and platelet-aggregatory properties under physiological flow conditions in vitro. In vivo studies in a mouse model demonstrated that PLNs accumulate at the wound site and induce ∼65% reduction in bleeding time, effectively mimicking and improving the hemostatic functions of natural platelets. We show that both the biochemical and biophysical design parameters of PLNs are essential in mimicking platelets and their hemostatic functions. PLNs offer a nanoscale technology that integrates platelet-mimetic biophysical and biochemical properties for potential applications in injectable synthetic hemostats and vascularly targeted payload delivery.

Cell-to-cell communication is not limited to a sender releasing a signaling molecule and a receiver perceiving it but is often self-regulated and bidirectional. Yet, in communities of synthetic cells, such features that render communication efficient and adaptive are missing. Here, we report the design and implementation of adaptive two-way signaling with lipid-vesicle-based synthetic cells. The first layer of self-regulation derives from coupling the temporal dynamics of the signal, H 2 O 2 , production in the sender to adhesions between sender and receiver cells. This way the receiver stays within the signaling range for the duration sender produces the signal and detaches once the signal fades. Specifically, H 2 O 2 acts as both a forward signal and a regulator of the adhesions by activating photoswitchable proteins at the surface for the duration of the chemiluminescence. The second layer of self-regulation arises when the adhesions render the receiver permeable and trigger the release of a backward signal, resulting in bidirectional exchange. These design rules provide a concept for engineering multicellular systems with adaptive communication.

Artificial cells are constructed to imitate natural cells and allow researchers to explore biological process and the origin of life. The construction methods for artificial cells, through both top-down or bottom-up approaches, have achieved great progress over the past decades. Here we present a comprehensive overview on the development of artificial cells and their properties and applications. Artificial cells are derived from lipids, polymers, lipid/polymer hybrids, natural cell membranes, colloidosome, metal-organic frameworks and coacervates. They can be endowed with various functions through the incorporation of proteins and genes on the cell surface or encapsulated inside of the cells. These modulations determine the properties of artificial cells, including producing energy, cell growth, morphology change, division, transmembrane transport, environmental response, motility and chemotaxis. Multiple applications of these artificial cells are discussed here with a focus on therapeutic applications. Artificial cells are used as carriers for materials and information exchange and have been shown to function as targeted delivery systems of personalized drugs. Additionally, artificial cells can function to substitute for cells with impaired function. Enzyme therapy and immunotherapy using artificial cells have been an intense focus of research. Finally, prospects of future development of cell-mimic properties and broader applications are highlighted.