Synthetic and living micropropellers for convection-enhanced nanoparticle transport

Nanoparticles (NPs) have emerged as an advantageous drug delivery platform for the treatment of various ailments including cancer and cardiovascular and inflammatory diseases. However, their efficacy in shuttling materials to diseased tissue is hampered by a number of physiological barriers. One hurdle is transport out of the blood vessels, compounded by difficulties in subsequent penetration into the target tissue. Here, we report the use of two distinct micropropellers powered by rotating magnetic fields to increase diffusion-limited NP transport by enhancing local fluid convection. In the first approach, we used a single synthetic magnetic microrobot called an artificial bacterial flagellum (ABF), and in the second approach, we used swarms of magnetotactic bacteria (MTB) to create a directable “living ferrofluid” by exploiting ferrohydrodynamics. Both approaches enhance NP transport in a microfluidic model of blood extravasation and tissue penetration that consists of microchannels bordered by a collagen matrix.ISSN:2375-254

Synthetic Circuit-Driven Expression of Heterologous Enzymes for Disease Detection

The integration of nanotechnology and synthetic biology could lay the framework for new classes of engineered biosensors that produce amplified readouts of disease states. As a proof-of-concept demonstration of this vision, here we present an engineered gene circuit that, in response to cancer-associated transcriptional deregulation, expresses heterologous enzyme biomarkers whose activity can be measured by nanoparticle sensors that generate amplified detection readouts. Specifically, we designed an AND-gate gene circuit that integrates the activity of two ovarian cancer-specific synthetic promoters to drive the expression of a heterologous protein output, secreted Tobacco Etch Virus (TEV) protease, exclusively from within tumor cells. Nanoparticle probes were engineered to carry a TEV-specific peptide substrate in order to measure the activity of the circuit-generated enzyme to yield amplified detection signals measurable in the urine or blood. We applied our integrated sense-and-respond system in a mouse model of disseminated ovarian cancer, where we demonstrated measurement of circuit-specific TEV protease activity both in vivo using exogenously administered nanoparticle sensors and ex vivo using quenched fluorescent probes. We envision that this work will lay the foundation for how synthetic biology and nanotechnology can be meaningfully integrated to achieve next-generation engineered biosensors