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Immunotherapies have revolutionized cancer treatment. These treatments rely on immune cell activation in tumours, which limits the number of patients that respond. Inflammatory molecules, like lipopolysaccharides (LPS), can activate innate immune cells, which convert tumour microenvironments from cold to hot, and increase therapeutic efficacy. However, systemic delivery of lipopolysaccharides (LPS) can induce cytokine storm. In this work, we developed immune‐controlling Salmonella (ICS) that only produce LPS in tumours after colonization and systemic clearance. We tuned the expression of msbB, which controls production of immunogenic LPS, by optimizing its ribosomal binding sites and protein degradation tags. This genetic system induced a controllable inflammatory response and increased dendritic cell cross‐presentation in vitro. The strong off state did not induce TNFα production and prevented adverse events when injected into mice. The accumulation of ICS in tumours after intravenous injection focused immune responses specifically to tumours. Tumour‐specific expression of msbB increased infiltration of immune cells, activated monocytes and neutrophils, increased tumour levels of IL‐6, and activated CD8 T cells in draining lymph nodes. These immune responses reduced tumour growth and increased mouse survival. By increasing the efficacy of bacterial anti‐cancer therapy, localized production of LPS could provide increased options to patients with immune‐resistant cancers. [ABSTRACT FROM AUTHOR]

This article describes a teaching module designed to enhance engineering creativity in an introductory chemical engineering course. The module includes an exercise to design column packing material, and an open-ended research project to describe the societal impact of chemical engineering. These assignments were created to illustrate the benefit of generating many ideas independent of analysis. The results of two years of survey-based assessment showed that these techniques improved students' confidence and ability with creative problems. (Contains 5 figures and 3 tables.)

Combining the specificity of tumor‐targeting bacteria with the sensitivity of biomarker detection would create a screening method able to detect small tumors and metastases. To create this system, we genetically modified an attenuated strain of Salmonella enterica to release a recombinant fluorescent biomarker (or fluoromarker). Salmonella expressing ZsGreen were intravenously administered to tumor‐bearing mice and fluoromarker production was induced after 48 hr. The quantities and locations of bacteria and ZsGreen were measured in tumors, livers and spleens by immunofluorescence, and the plasma concentration of ZsGreen was measured using single‐layer ELISA. In the plasma, the ZsGreen concentration was in the range of 0.5–1.5 ng/ml and was dependent on tumor mass (with a proportion of 0.81 ± 0.32 ng·ml−1·g−1). No adverse reaction to ZsGreen or bacteria was observed in any mice. ZsGreen was released at an average rate of 4.3 fg·CFU−1·hr−1 and cleared from the plasma with a rate constant of 0.259 hr−1. ZsGreen production was highest in viable tissue (7.6 fg·CFU−1·hr−1) and lowest in necrotic tissue (0.47 fg·CFU−1·hr−1). The mass transfer rate constant from tumor to blood was 0.0125 hr−1. Based on these measurements, this system has the capability to detect tumors as small as 0.12 g. These results demonstrate four essential mechanisms of this method: (i) preferential tumor colonization by bacteria, (ii) fluoromarker release in vivo, (iii) fluoromarker transport through tumor tissue and (iv) slow enough systemic clearance to enable measurement. This bacteria‐based blood test would be minimally invasive and has the potential to identify previously undetectable microscopic tumors. What's new? Facultative anaerobic bacteria readily colonize solid tumors. The diffusion into the bloodstream of a fluorescent marker released by these organisms as they proliferate inside a tumor could facilitate cancer detection. Here, an engineered bacterial system employing a fluoromarker‐producing attenuated strain of Salmonella enterica demonstrated capability in detecting tumor volumes of 0.12 grams in mice. This tumor size is comparable to the smallest tumors detected by tomographic imaging. The experiments provide insight into mechanisms underlying bacterial tumor colonization, fluoromarker release in vivo, and fluoromarker transport through tumor tissue. Fluoromarker tissue transport and systemic clearance was gradual, enabling measurement in blood plasma. [ABSTRACT FROM AUTHOR]

A study is conducted to demonstrate that glutathione (GSH) serves as an effective trigger to release a payload (dye molecules) from nanoparticle surfaces both in vitro and in cell cultures. It is noted that the GSH-mediated release, combined with the controlled interactions of biomolecules with surface functionalised nano-particle scaffolds, can be further utilized to realize delivery of proteins and enhance transfection of genetic materials.