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In this study, we report the microfluidic-based synthesis of a multifunctional Janus hydrogel particle with anisotropic superparamagnetic properties and chemical composition for the bottom-up assembly of hydrogel superstructures. In a uniform magnetic field, the resulting Janus magnetic particles fabricated in the present method exhibit chainlike or meshlike superstructure forms, the complexity of which can be simply modulated by particle density and composition. This controllable field-driven assembly of the particles can be potentially used as building blocks to construct targeted superstructures for tissue engineering. More importantly, we demonstrated that this method also shows the ability to generate multifunctional Janus particles with great design flexibilities: (a) direct encapsulation and precise spatial distribution of biological substance and (b) selective surface functionalization in a particle. Although these monodisperse particles find immediate use in tissue engineering, their ability to self-assemble with tunable anisotropic configurations makes them an intriguing material for several exciting areas of research such as photonic crystals, novel microelectronic architecture, and sensing.

Assembly-line polyketide synthases (PKSs) are among the most complex protein machineries known in nature, responsible for the biosynthesis of numerous compounds used in the clinic. Their present-day diversity is the result of an evolutionary path that has involved the emergence of a multimodular architecture and further diversification of assembly-line PKSs. In this review, we provide an overview of previous studies that investigated PKS evolution and propose a model that challenges the currently prevailing view that gene duplication has played a major role in the emergence of multimodularity. We also analyze the ensemble of orphan PKS clusters sequenced so far to evaluate how large the entire diversity of assembly-line PKS clusters and their chemical products could be. Finally, we examine the existing techniques to access the natural PKS diversity in natural and heterologous hosts and describe approaches to further expand this diversity through engineering.

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There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (i) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (ii) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50-150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance.T he field of nanotechnology has crossed significant milestones from the systemic delivery of nanomedicines (1-5). However, the ability to achieve spatiotemporal control may be essential to many medical applications.In this study, we engineer a nanoparticle (NP) system that fundamentally changes the way we control spatiotemporal delivery of therapeutic agents. We designed approximately 60-nm core-shell hybrid NPs (6, 7) consisting of a polymeric core, a lipid interface, and a poly(ethylene glycol) (PEG) corona. For temporal control, we achieved the capacity for slow drug elution over 2 weeks using poly(lactic acid) (PLA) conjugates of paclitaxel as a model therapeutic agent (8), made by a modified drug-alkoxide ring-opening strategy (9, 10). These conjugates allow for controlled drug release by gradual ester hydrolysis despite the large surface area and short diffusion distances of sub-100-nm particles. For spatial control, we functionalized our NPs with ligands (11, 12) that target across a range of diseases in a consistent and reproducible manner. Conventional molecular targeting of relevant cell-based targets can be confounded by inter-and intrapatient heterogeneity in cell surface antigen expression (13,14). More recently, investigators have explored abundant noncellular targets such as the coagulation cascade (15), intraarticular cartilage (16), and extracellular matrix (17). Many human diseases are associated with compromised vasculature and increased vascular permeability (18,19). Therefore, we exploit these vascular breaches by targeting the underlying basement membrane. Toward this goal, we screened for heptapeptide ligands by biopanning a phage library against collagen IV (20), which represents 50% of the vascular basement membrane (21), and characterized specific ligands for targeting affinity against...