Optoregulated Drug Release from an Engineered Living Material: Self‐Replenishing Drug Depots for Long‐Term, Light‐Regulated Delivery

Abstract

On‐demand and long‐term delivery of drugs are common requirements in many therapeutic applications, not easy to be solved with available smart polymers for drug encapsulation. This work presents a fundamentally different concept to address such scenarios using a self‐replenishing and optogenetically controlled living material. It consists of a hydrogel containing an active endotoxin‐free Escherichia coli strain. The bacteria are metabolically and optogenetically engineered to secrete the antimicrobial and antitumoral drug deoxyviolacein in a light‐regulated manner. The permeable hydrogel matrix sustains a viable and functional bacterial population and permits diffusion and delivery of the synthesized drug to the surrounding medium at quantities regulated by light dose. Using a focused light beam, the site for synthesis and delivery of the drug can be freely defined. The living material is shown to maintain considerable levels of drug production and release for at least 42 days. These results prove the potential and flexibility that living materials containing engineered bacteria can offer for advanced therapeutic applications.

Light-Inducible Recombinases for Bacterial Optogenetics

“…As examples, light has been used to control expression of enzymes involved in biofuel synthesis 13,14 and to regulate bacterial growth via metabolic control. 15,16 In addition, it has been used to enable light-activated drug release from hydrogels 17 and patterning of Escherichia coli onto multiple materials, 18 indicative of the wide ranging potential of optogenetic approaches. At present, the current bacterial optogenetic toolset primarily includes two-component systems 8,19,20 and split proteins.…”

Optogenetic Approaches for the Spatiotemporal Control of Signal Transduction Pathways

“…Recently, biodegradable polyethylene glycol diacrylate (PEGDA) linked with DL-dithiothreitol (DTT) could be used to photo induce cell migration and drug release, while being able to have its lifetime adjusted to the desired time frame of the application [ 104 ]. To take advantage of the unique abilities of optogenetics there have been different ideas for a possible application like the control of the blood homeostasis in mice [ 105 ], targeting cancer cells via light for T-cells [ 106 ], gene therapy approaches to tackle breast cancer [ 107 ], adenoviral based therapy to selectively target cancer cells with light and reduce off-target effects [ 108 , 109 ]. Combining therapeutic approaches with optogenetic may result in an improvement of the safety and anti-cancer selectivity, making it a promising addition to existing therapeutic approaches to enhance their effectiveness.…”

Synthetic biology as driver for the biologization of materials sciences

“…These strategies are based on the administration of material-embedded drug-producing bacteria or mammalian cells to provide sustained and patient-adapted delivery of therapeutic compounds. Recently, the Sankaran and Del Campo groups developed bacteria-based ELMs to produce therapeutic compounds in response to optical stimuli [ 274 , 275 ]. As host cells, endotoxin-free E. coli (ClearColi) were used, the outer membrane lipopolysaccharides of which have genetically been modified to avoid an endotoxin response in humans [ 276 ].…”