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Macrophages are specialized phagocytes that play central roles in immunity and tissue repair. Their diverse functionalities have led to an evolution of new allogenic and autologous macrophage products. However, realizing the full therapeutic potential of these cell‐based therapies requires development of imaging technologies that can track immune cell migration within tissues in real‐time. Such innovations will not only inform treatment regimens and empower interpretation of therapeutic outcomes but also enable prediction and early intervention during adverse events. Here, phase‐changing nanoemulsion contrast agents are reported that permit real‐time, continuous, and high‐fidelity ultrasound imaging of macrophages in situ. Using a de novo designed peptide emulsifier, liquid perfluorocarbon nanoemulsions are prepared and show that rational control over interfacial peptide assembly affords formulations with tunable acoustic sensitivity, macrophage internalization, and in cellulo stability. Imaging experiments demonstrate that emulsion‐loaded macrophages can be readily visualized using standard diagnostic B‐mode and Doppler ultrasound modalities. This allows on‐demand and long‐term tracking of macrophages within porcine coronary arteries, as an exemplary model. The results demonstrate that this platform is poised to open new opportunities for non‐invasive, contrast‐enhanced imaging of cell‐based immunotherapies in tissues, while leveraging the low‐cost, portable, and safe nature of diagnostic ultrasound. 

Abstract Interfacial self‐assembly describes the directed organization of molecules and colloids at phase boundaries. Believed to be fundamental to the inception of primordial life, interfacial assembly is exploited by a myriad of eukaryotic and prokaryotic organisms to execute physiologic activities and maintain homeostasis. Inspired by these natural systems, chemists, engineers, and materials scientists have sought to harness the thermodynamic equilibria at phase boundaries to create multi‐dimensional, highly ordered, and functional nanomaterials. Recent advances in our understanding of the biophysical principles guiding molecular assembly at gas–solid, gas–liquid, solid–liquid, and liquid–liquid interphases have enhanced the rational design of functional bio‐nanomaterials, particularly in the fields of biosensing, bioimaging and biotherapy. Continued development of non‐canonical building blocks, paired with deeper mechanistic insights into interphase self‐assembly, holds promise to yield next generation interfacial bio‐nanomaterials with unique, and perhaps yet unrealized, properties. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Emerging Technologies 

Abstract The human colon is home to trillions of microorganisms that modulate gastrointestinal physiology. The understanding of how this gut ecosystem impacts human health, although evolving, is slowed by the lack of accessible tools suitable to studying complex host‐mucus‐microbe interactions. Here, a synthetic gel‐like material capable of recapitulating the varied structural, mechanical, and biochemical profiles of native human colonic mucus is reported to develop compositionally simple microbiome screening platforms with utility in microbiology and drug discovery. The viscous fibrillar material is realized through templated assembly of a fluorine‐rich amino acid at liquid‐liquid interphases. The fluorine‐assisted mucus surrogate (FAMS) can be decorated with mucins to serve as a habitat for microbial colonization and integrated with human colorectal cells to generate artificial mucosae, referred to as a microbiome organoid. Notably, FAMS are made with inexpensive and commercially available materials and can be generated using simple protocols and standard laboratory hardware. As a result, this platform can be broadly incorporated into various laboratory settings to advance probiotic research and inform in vivo approaches. If implemented into high throughput screening approaches, FAMS may represent a valuable tool to study compound metabolism and gut permeability, with an exemplary demonstration of this utility presented here. 

Abstract Fluorinated compounds, while rarely used by nature, are emerging as fundamental ingredients in biomedical research, with applications in drug discovery, metabolomics, biospectroscopy, and, as the focus of this review, peptide/protein engineering. Leveraging the fluorous effect to direct peptide assembly has evolved an entirely new class of organofluorine building blocks from which unique and bioactive materials can be constructed. Here, we discuss three distinct peptide fluorination strategies used to design and induce peptide assembly into nano‐, micro‐, and macro‐supramolecular states that potentiate high‐ordered organization into material scaffolds. These fluorine‐tailored peptide assemblies employ the unique fluorous environment to boost biofunctionality for a broad range of applications, from drug delivery to antibacterial coatings. This review provides foundational tactics for peptide fluorination and discusses the utility of these fluorous‐directed hierarchical structures as material platforms in diverse biomedical applications.