Mahama A. Traore
Bio: Mahama A. Traore is an academic researcher from Virginia Tech. The author has contributed to research in topics: Drug delivery & Chemotaxis. The author has an hindex of 6, co-authored 13 publications receiving 220 citations.
TL;DR: It is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100‐fold without requiring any externally applied driving force or control input.
Abstract: Cancer drug delivery remains a formidable challenge due to systemic toxicity and inadequate extravascular transport of nanotherapeutics to cells distal from blood vessels. It is hypothesized that, in absence of an external driving force, the Salmonella enterica serovar Typhimurium could be exploited for autonomous targeted delivery of nanotherapeutics to currently unreachable sites. To test the hypothesis, a nanoscale bacteria-enabled autonomous drug delivery system (NanoBEADS) is developed in which the functional capabilities of the tumor-targeting S. Typhimurium VNP20009 are interfaced with poly(lactic-co-glycolic acid) nanoparticles. The impact of nanoparticle conjugation is evaluated on NanoBEADS' invasion of cancer cells and intratumoral transport in 3D tumor spheroids in vitro, and biodistribution in a mammary tumor model in vivo. It is found that intercellular (between cells) self-replication and translocation are the dominant mechanisms of bacteria intratumoral penetration and that nanoparticle conjugation does not impede bacteria's intratumoral transport performance. Through the development of new transport metrics, it is demonstrated that NanoBEADS enhance nanoparticle retention and distribution in solid tumors by up to a remarkable 100-fold without requiring any externally applied driving force or control input. Such autonomous biohybrid systems could unlock a powerful new paradigm in cancer treatment by improving the therapeutic index of chemotherapeutic drugs and minimizing systemic side effects.
TL;DR: This work utilizes a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigates the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles, demonstrating for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport.
Abstract: Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).
TL;DR: In this work, theoretical and experimental investigations of chemotactic motility of a 10 μm diameter microbead propelled by an ensemble of attached flagellated bacteria are presented and close agreement between theory and experiments demonstrates the possibility of using the presented model as a predictive tool for other similar biohybrid systems.
Abstract: Micro-objects propelled by whole cell actuators, such as flagellated bacteria, are being increasingly studied and considered for a wide variety of applications. In this work we present theoretical and experimental investigations of chemotactic motility of a 10 μm diameter microbead propelled by an ensemble of attached flagellated bacteria. The stochastic model presented here encompasses the behavior of each individual bacterium attached to the microbead in a spatiotemporally varying chemoattractant field. The computational model shows that in a chemotactic environment, the ensemble of bacteria, although constrained, propel the bead in a chemotactic manner with a 67% enhancement in displacement to distance ratio (defined as directionality) compared to nonchemotactic propulsion. The simulation results are validated experimentally. Close agreement between theory and experiments demonstrates the possibility of using the presented model as a predictive tool for other similar biohybrid systems.
TL;DR: Using the microfabrication and characterization methodology presented in this work, microfluidic platforms with well-defined and customizable diffusive properties can be developed to accommodate the study of a wide range of cell types.
Abstract: The study of cells in a well-defined and chemically programmable microenvironment is essential for a complete and fundamental understanding of the cell behaviors with respect to specific chemical compounds. Flow-free microfluidic devices that generate quasi-steady chemical gradients (spatially varying but temporally constant) have been demonstrated as effective chemotaxis assay platforms due to dissociating the effect of chemical cues from mechanical shear forces caused by fluid flow. In this work, we demonstrate the fabrication and characterization of a flow-free microfluidic platform made of polyethylene glycol diacrylate (PEG-DA) hydrogel. We have demonstrated that the mass transport properties of these devices can be customized by fabricating them from PEG-DA gels of four distinct molecular weights. In contrast to microfluidic devices developed using soft lithography; this class of devices can be realized using a more cost-effective approach of direct photopolymerization with fewer microfabrication steps. This microfluidic platform was tested by conducting a quantitative study of the chemotactic behavior of Escherichia coli (E. coli) RP437, a model microorganism, in presence of the chemo-effector, casamino-acids. Using the microfabrication and characterization methodology presented in this work, microfluidic platforms with well-defined and customizable diffusive properties can be developed to accommodate the study of a wide range of cell types.
TL;DR: A simple and cost-effective sorting technique for separation of similarly-sized particles of dissimilar surface properties within a diffusion-based microfluidic platform using chemotaxis in Escherichia coli bacteria is reported.
Abstract: High throughput sorting of micro/nanoparticles of similar sizes is of significant interest in many biological and chemical applications. In this work, we report a simple and cost-effective sorting technique for separation of similarly-sized particles of dissimilar surface properties within a diffusion-based microfluidic platform using chemotaxis in Escherichia coli bacteria. Differences in surface chemistry of two groups of similarly-sized nanoparticles in a mixture were exploited to selectively assemble one particle group onto motile E. coli, through either specific or non-specific adhesion, and separate them from the remaining particle group via chemotaxis of the attached bacteria. To enable optimal operation of the sorting platform, the chemotaxis behavior of E. coli bacteria in response to casamino acids, the chemoeffector of choice was first characterized. The chemical concentration gradient range within which the bacteria exhibit a positive chemotactic response was found to be within 0.25 × 10−7–1.0 × 10−3 g ml−1 mm−1. We demonstrate that at the optimum concentration gradient of 5.0 × 10−4 g ml−1 mm−1, a sorting efficiency of up to 81% at a throughput of 2.4 × 105 particles per min can be achieved. Sensitivity of the sorting efficiency to the adhesion mechanism and particle size in the range of 320–1040 nm was investigated.
TL;DR: The promises and challenges of employing bioengineered bacteria in drug delivery systems are reviewed, the biohybrid design concept is introduced as a new additional paradigm in bacteria-based drug delivery and the design of unique, complex therapeutic functions are introduced.
Abstract: The use of bacterial cells as agents of medical therapy has a long history. Research that was ignited over a century ago with the accidental infection of cancer patients has matured into a platform technology that offers the promise of opening up new potential frontiers in medical treatment. Bacterial cells exhibit unique characteristics that make them well-suited as smart drug delivery agents. Our ability to genetically manipulate the molecular machinery of these cells enables the customization of their therapeutic action as well as its precise tuning and spatio-temporal control, allowing for the design of unique, complex therapeutic functions, unmatched by current drug delivery systems. Early results have been promising, but there are still many important challenges that must be addressed. We present a review of promises and challenges of employing bioengineered bacteria in drug delivery systems and introduce the biohybrid design concept as a new additional paradigm in bacteria-based drug delivery.
TL;DR: The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening.
Abstract: The natural microenvironment of tumors is composed of extracellular matrix (ECM), blood vasculature, and supporting stromal cells. The physical characteristics of ECM as well as the cellular components play a vital role in controlling cancer cell proliferation, apoptosis, metabolism, and differentiation. To mimic the tumor microenvironment outside the human body for drug testing, two-dimensional (2-D) and murine tumor models are routinely used. Although these conventional approaches are employed in preclinical studies, they still present challenges. For example, murine tumor models are expensive and difficult to adopt for routine drug screening. On the other hand, 2-D in vitro models are simple to perform, but they do not recapitulate natural tumor microenvironment, because they do not capture important three-dimensional (3-D) cell–cell, cell–matrix signaling pathways, and multi-cellular heterogeneous components of the tumor microenvironment such as stromal and immune cells. The three-dimensional (3-D) in vitro tumor models aim to closely mimic cancer microenvironments and have emerged as an alternative to routinely used methods for drug screening. Herein, we review recent advances in 3-D tumor model generation and highlight directions for future applications in drug testing.
TL;DR: This Account will summarize the effort and those of other groups, in the design and development of self-propelled colloids of different structural properties and powered by different propulsion mechanisms, and briefly address the applications that have been proposed and demonstrated for these swimmer designs.
Abstract: ConspectusSelf-propelled colloids have emerged as a new class of active matter over the past decade. These are micrometer sized colloidal objects that transduce free energy from their surroundings and convert it to directed motion. The self-propelled colloids are in many ways, the synthetic analogues of biological self-propelled units such as algae or bacteria. Although they are propelled by very different mechanisms, biological swimmers are typically powered by flagellar motion and synthetic swimmers are driven by local chemical reactions, they share a number of common features with respect to swimming behavior. They exhibit run-and-tumble like behavior, are responsive to environmental stimuli, and can even chemically interact with nearby swimmers. An understanding of self-propelled colloids could help us in understanding the complex behaviors that emerge in populations of natural microswimmers. Self-propelled colloids also offer some advantages over natural microswimmers, since the surface properties, p...
TL;DR: The recent advances in nanoparticle separation using microfluidic devices are reviewed, focusing on its techniques, its advantages over conventional methods, and its potential applications, as well as foreseeable challenges in the separation of synthetic nanoparticles and biological molecules.
Abstract: Nanoparticles have been widely implemented for healthcare and nanoscience industrial applications Thus, efficient and effective nanoparticle separation methods are essential for advancement in these fields However, current technologies for separation, such as ultracentrifugation, electrophoresis, filtration, chromatography, and selective precipitation, are not continuous and require multiple preparation steps and a minimum sample volume Microfluidics has offered a relatively simple, low-cost, and continuous particle separation approach, and has been well-established for micron-sized particle sorting Here, we review the recent advances in nanoparticle separation using microfluidic devices, focusing on its techniques, its advantages over conventional methods, and its potential applications, as well as foreseeable challenges in the separation of synthetic nanoparticles and biological molecules, especially DNA, proteins, viruses, and exosomes
TL;DR: The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale.
Abstract: As we move towards the miniaturization of devices to perform tasks at the nano and microscale, it has become increasingly important to develop new methods for actuation, sensing, and control. Over the past decade, bio-hybrid methods have been investigated as a promising new approach to overcome the challenges of scaling down robotic and other functional devices. These methods integrate biological cells with artificial components and therefore, can take advantage of the intrinsic actuation and sensing functionalities of biological cells. Here, the recent advancements in bio-hybrid actuation are reviewed, and the challenges associated with the design, fabrication, and control of bio-hybrid microsystems are discussed. As a case study, focus is put on the development of bacteria-driven microswimmers, which has been investigated as a targeted drug delivery carrier. Finally, a future outlook for the development of these systems is provided. The continued integration of biological and artificial components is envisioned to enable the performance of tasks at a smaller and smaller scale in the future, leading to the parallel and distributed operation of functional systems at the microscale.