A programmable oral bacterial hydrogel for controllable production and release of nanovaccine for tumor immunotherapy.

Oral protein vaccines are mainly used to prevent the infection of intestinal pathogens in clinic due to their high safety and strong compliance. However, it is necessary to design the efficient delivery systems to overcome the harsh gastrointestinal environment in the application process. Here we established a programmable oral bacterial hydrogel system for spatiotemporally controllable production and release of nanovaccines. The system was divided into three parts: (1) Engineered bacteria were encapsulated in chitosan-sodium alginate microcapsules, which offered protection against the extreme acid conditions in the stomach. (2) Microcapsules were dissolved, and then engineered bacteria were released and colonized in the intestine. (3) The release of nanovaccines was controlled periodically by a synchronous lysis genetic circuit for tumor immunotherapy. Compared to control groups, tumor volume of subcutaneous tumor-bearing mice treated with bacterial microgels releasing optimized nanovaccine was almost inhibited by 75% and T cell response was activated at least 2-fold. We believe that this programmable bacterial hydrogel will offer a promising way for the application of oral nanovaccines.

Hydrogel microcapsules containing engineered bacteria for sustained production and release of protein drugs.

Subcutaneous administration of sustained-release formulations is a common strategy for protein drugs, which avoids first pass effect and has high bioavailability. However, conventional sustained-release strategies can only load a limited amount of drug, leading to insufficient durability. Herein, we developed microcapsules based on engineered bacteria for sustained release of protein drugs. Engineered bacteria were carried in microcapsules for subcutaneous administration, with a production-lysis circuit for sustained protein production and release. Administrated in diabetic rats, engineered bacteria microcapsules was observed to smoothly release Exendin-4 for 2 weeks and reduce blood glucose. In another example, by releasing subunit vaccines with bacterial microcomponents as vehicles, engineered bacterial microcapsules activated specific immunity in mice and achieved tumor prevention. The engineered bacteria microcapsules have potential to durably release protein drugs and show versatility on the size of drugs. It might be a promising design strategy for long-acting in situ drug factory.

Optotheranostic Nanosystem with Phone Visual Diagnosis and Optogenetic Microbial Therapy for Ulcerative Colitis At-Home Care.

Ulcerative colitis (UC) is a relapsing disorder characterized by chronic inflammation of the intestinal tract. However, the home care of UC based on remote monitoring, due to the operational complexity and time-consuming procedure, restrain its widespread applications. Here we constructed an optotheranostic nanosystem for self-diagnosis and long-acting mitigations of UC at home. The system included two major modules: (i) A disease prescreening module mediated by smartphone optical sensing. (ii) Disease real-time intervention module mediated by an optogenetic engineered bacteria system. Recombinant Escherichia coli Nissle 1917 (EcN) secreted interleukin-10 (IL-10) could downregulate inflammatory cascades and matrix metalloproteinases; it is a candidate for use in the therapeutic intervention of UC. The results showed that the Detector was able to analyze, report, and share the detection results in less than 1 min, and the limit of detection was 15 ng·mL-1. Besides, the IL-10-secreting EcN treatment suppressed the intestinal inflammatory response in UC mice and protected the intestinal mucosa against injury. The optotheranostic nanosystems enabled solutions to diagnose and treat disease at home, which promotes a mobile health service development.