Synthetic glycans control gut microbiome structure and mitigate colitis in mice.

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. Here, we study the properties and therapeutic potential of chemically diverse synthetic glycans (SGs).

A New Approach to Modify Plant Microbiomes and Traits by Introducing Beneficial Bacteria at Flowering into Progeny Seeds.

The microbial component of healthy seeds - the seed microbiome - appears to be inherited between plant generations and can dynamically influence germination, plant performance, and survival. As such, methods to optimize the seed microbiomes of major crops could have far-reaching implications for plant breeding and crop improvement to enhance agricultural food, feed, and fiber production. Here, we describe a new approach to modulate seed microbiomes of elite crop seed embryos and concomitantly design the traits to be mediated by seed microbiomes.

Nanoparticle amplification photothermal unveiling of cryptic collagen binding sites.

The success of nanoparticle-based cancer therapies ultimately depends on their ability to selectively and efficiently accumulate in regions of disease. Outfitting nanoparticles to actively target tumor-specific markers has improved specificity, yet it remains a challenge to amass adequate therapy in a selective manner. To help address this challenge, we have developed a mechanism of nanoparticle amplification based on stigmergic (environment-modifying) signalling, in which a "Signalling" population of gold nanorods induces localized unveiling of cryptic collagen epitopes, which are in turn targeted by "Responding" nanoparticles bearing gelatin-binding fibronectin fragments.

Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease.

Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry.

Nanoparticles that communicate in vivo to amplify tumour targeting.

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of 'signalling' modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted 'receiving' nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery.

Ligand-clustered "patchy" nanoparticles for modulated cellular uptake and in vivo tumor targeting.

Despite the evident success of using a multivalent approach to increase efficacy of targeted delivery, a clear understanding of how multiple ligands behave collectively to influence the uptake of nanoparticle cell-targeting agents has not been reached. Although when present in large quantity, multivalent ligands can increase binding avidities to cells, it is also conceivable, that the manner in which these ligands are presented to the cell may have a significant effect on uptake. Here we examine this parameter using a linear dendritic polymer construct that enabled us to pattern the surfaces of nanoparticles with variable sized ligand clusters in different spatial arrangements.

Cooperative nanomaterial system to sensitize, target, and treat tumors.

A significant barrier to the clinical translation of systemically administered therapeutic nanoparticles is their tendency to be removed from circulation by the mononuclear phagocyte system. The addition of a targeting ligand that selectively interacts with cancer cells can improve the therapeutic efficacy of nanomaterials, although these systems have met with only limited success. Here, we present a cooperative nanosystem consisting of two discrete nanomaterials.

Functional delivery of siRNA in mice using dendriworms.

Small interfering RNAs (siRNAs) mediate cleavage of specific, complementary mRNA sequences and thus regulate gene expression. Not surprisingly, their use for treatment of diseases that are rooted in aberrant gene expression, such as cancer, has become a paradigm that has gained wide interest. Here, we report the development of dendrimer-conjugated magnetofluorescent nanoworms that we call "dendriworms" as a modular platform for siRNA delivery in vivo.

Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas.

Plasmonic nanomaterials have the opportunity to considerably improve the specificity of cancer ablation by i.v. homing to tumors and acting as antennas for accepting externally applied energy.

Systematic surface engineering of magnetic nanoworms for in vivo tumor targeting.

In the design of nanoparticles that can target disease tissue in vivo, parameters such as targeting ligand density, type of target receptor, and nanoparticle shape can play an important role in determining the extent of accumulation. Herein, a systematic study of these parameters for the targeting of mouse xenograft tumors is performed using superparamagnetic iron oxide as a model nanoparticle system. The type of targeting peptide (recognizing cell surface versus extracellular matrix), the surface coverage of the peptide, its attachment chemistry, and the shape of the nanomaterial [elongated (nanoworm, NW) versus spherical (nanosphere, NS)] are varied.

Biodegradable luminescent porous silicon nanoparticles for in vivo applications.

Nanomaterials that can circulate in the body hold great potential to diagnose and treat disease. For such applications, it is important that the nanomaterials be harmlessly eliminated from the body in a reasonable period of time after they carry out their diagnostic or therapeutic function. Despite efforts to improve their targeting efficiency, significant quantities of systemically administered nanomaterials are cleared by the mononuclear phagocytic system before finding their targets, increasing the likelihood of unintended acute or chronic toxicity.

In vivo tumor cell targeting with "click" nanoparticles.

The in vivo fate of nanomaterials strongly determines their biomedical efficacy. Accordingly, much effort has been invested into the development of library screening methods to select targeting ligands for a diversity of sites in vivo. Still, broad application of chemical and biological screens to the in vivo targeting of nanomaterials requires ligand attachment chemistries that are generalizable, efficient, covalent, orthogonal to diverse biochemical libraries, applicable under aqueous conditions, and stable in in vivo environments.

Nanoparticle self-assembly gated by logical proteolytic triggers.

[Image: see text] The emergent electromagnetic properties of nanoparticle self-assemblies are being harnessed to build new medical and biochemical assays with unprecedented sensitivity. While current self-assembly assays have displayed superior sensitivity for single molecular targets, development of systems with the capacity to process multiple inputs may more effectively decipher complex disease signatures such as cancer. Herein, we present the design and synthesis of nanoparticles that utilize Boolean logic to simultaneously probe for two proteolytic inputs associated with unique aspects of tumorigenesis (MMP2 and MMP7).