bims-livmat 2026-08-16 papers

Research (Wash D C). 2026 ;9 1390

From Mechanism to Clinic: Engineered Bacteria-Nanomaterial Hybrid Systems for Cancer Immunotherapy.

Jia Lin, Mingxin An, Yuxin Dai, Yuanting Huang, Zhijun Li, Pin Yao, Huizhe Wu, Dake Xu, Xiaoqian Xu.

Hypoxia, immunosuppression, and pronounced heterogeneity within the tumor microenvironment (TME) hinder the effectiveness of cancer therapies. Engineered bacteria-nanomaterial hybrid systems have emerged as a promising approach to address these challenges. Bacterial chassis provide active tumor targeting, deep tissue penetration, and in situ proliferation, facilitating the precise delivery of immunomodulators. Concurrently, nanomaterials interfaced with these living carriers can be activated by external physical stimuli, inducing photothermal, photodynamic, sonodynamic, and magnetothermal effects within solid tumors. These interactions promote immunogenic cell death (ICD) and enable real-time monitoring. Recent advances in synthetic biology and nanotechnology have led to the development of an expanding range of preclinical biohybrid platforms, while several related components, including bacterial therapeutics, bacterial derivatives, and physically activated nanomedicine platforms, have progressed into clinical evaluation. This review first explores the origins and roles of tumor-associated bacteria. It then summarizes strategies for engineering bacteria-nanomaterial hybrid systems. Subsequently, this review examines how physical stimuli enhance targeting, remodel the TME, and amplify antitumor immunity. Finally, safety, manufacturing, and regulatory challenges impacting clinical translation are discussed. Overall, these platforms offer a potentially powerful framework for precision cancer immunotherapy. However, successful clinical translation will require stronger evidence regarding safety, controllability, manufacturing consistency, and therapeutic efficacy.

DOI: https://doi.org/10.34133/research.1390

Nature. 2026 Aug 12.

Glucose-responsive probiotics for glycaemic modulation in mice and monkeys.

Ningzi Guan, Deqiang Kong, Xianyun Gao, Lingxue Niu, Yang Zhou, Guiling Yu, Tian Gao, Mengyao Liu, Wenbo Ma, Yiyu Jin, Jianli Yin, Shangang Zhao, Haifeng Ye.

Sustained and controlled delivery of glucose-lowering agents using engineered designer cells is recognized as an effective strategy for diabetes therapy1. However, current technologies rely on external signal control or have been programmed into mammalian cells using synthetic gene networks, which pose safety concerns arising from transplantation2,3. Here we developed an engineered oral-deliverable glucose-sensing and functional response probiotic living drug for 'sense-and-respond'-based control of diabetic blood glucose. We created a glucose sensor based on a synthetic gene circuit that incorporates the glucose-responsive transcriptional regulator HexR, coupled with a synthetic promoter. Upon oral administration of the engineered probiotics carrying the sensor, the cells reside temporarily in the intestine and regulate the expression of therapeutic transgenes in response to glucose levels that exceed the normal threshold. We show efficacy from the engineered probiotics for glycaemic control in multiple diabetic mouse and non-human primate models, demonstrating that long-term oral administration drives clear improvements in lipid profiles, while also attenuating development of multiple diabetic complications. Our probiotics-based living drug enables therapeutic dosing in response to real-time blood glucose levels, providing a programmable, orally deliverable sense-and-respond platform for metabolic therapy without transplantation.

DOI: https://doi.org/10.1038/s41586-026-10909-6

Trends Biotechnol. 2026 Aug 14. pii: S0167-7799(26)00329-X. [Epub ahead of print]

Empowering microbes with natural armor: encapsulation strategies for agri-food and biotech innovations.

Simona Cioffi, Michele Iafisco, Alessio Adamiano.

Encapsulation enables microbial technologies across agriculture, biotechnology, and biomedicine by protecting microorganisms from environmental and process-related stresses while extending their functional performance. Natural materials, including polysaccharides such as alginate and chitosan, and biomineral nanoparticles, are emerging as key enablers of encapsulation performance, while supporting sustainability, scalability, and industrial implementation. In this review, we analyze recent advances in natural polymer- and biomineral-based encapsulation systems, focusing on how material selection, encapsulation architecture, and microbial metabolism shape engineered microenvironments. We further discuss how encapsulation becomes technologically and environmentally relevant only when functional gains justify material and processing costs. Finally, we argue for a conceptual shift in encapsulation strategies: from protective supports toward bioinspired microhabitats and living microcapsules capable of programmable microbial functions.

Keywords: bioinspired materials; biomineralization; microbial biocontrol; microbial encapsulation; natural polymers; sustainable biomanufacturing

DOI: https://doi.org/10.1016/j.tibtech.2026.07.030

Biomed Pharmacother. 2026 Aug 10. pii: S0753-3322(26)00874-7. [Epub ahead of print]202 119838

Engineered PEA-producing Lactobacillus paracasei F19 prevents colitis-associated colorectal cancer in mice by modulating inflammatory-angiogenic signaling and beneficially reshapes gut microbiota composition.

Irene Palenca, Walter Sanseverino, Roberto Malinverni, Martina Vincenzi, Giulia Beaufils, Vincenzo Romano Spica, Federica Valeriani, Giovanni Sarnelli, Giuseppe Esposito.

Colitis-associated colorectal cancer (CAC) arises from the interplay between chronic inflammation, epithelial dysregulation, angiogenesis, and microbiota alterations. Palmitoylethanolamide (PEA) is an endogenous lipid mediator with anti-inflammatory and anti-angiogenic properties, but despite its promise, insufficient bioavailability at the intestinal mucosa represents a major hurdle. We investigated whether local, sustained PEA delivery via an engineered Lactobacillus paracasei expressing N-acyl-phosphatidylethanolamine-specific phospholipase D (pNAPE-LP) could prevent CAC by targeting inflammatory, angiogenic, and microbial pathways. pNAPE-LP/palmitate markedly reduced mucosal damage and tumor burden compared with the AOM/DSS group, while naïve pLP and palmitate alone were ineffective. Treatment suppressed epithelial proliferation and angiogenesis, restored p53-wt expression, and significantly increased colonic PEA levels, confirming effective in situ biosynthesis. Mechanistically, pNAPE-LP inhibited activation of the Akt/mTOR/p70S6K pathway and reduced HIF-1α expression. Microbiota profiling revealed profound tumor-associated dysbiosis characterized by the collapse of dominant commensalsand expansion of pathobionts in the AOM/DSS group. pNAPE-LP induced a robust ecological remodeling, shifting beta-diversity toward healthy controls, restoring key genera associated with mucosal homeostasis, and suppressing taxa overrepresented in the tumor state. These effects were strictly dependent on PEA release following substrate administration, enabled by NAPE-PLD expression. Engineered pNAPE-LP acts as a living biotherapeutic that locally delivers PEA while simultaneously reprogramming inflammation, angiogenesis, oncogenic signaling, and microbiota composition. This multimodal mechanism effectively interrupts the pathogenic feedback loops driving CAC. Engineered PEA-producing probiotics represent a promising strategy for mucosa-targeted prevention of inflammation-associated colorectal cancer.

Keywords: Colorectal cancer; Engineered probiotics; Lactobacillus paracasei; Next generation probiotics; PEA

DOI: https://doi.org/10.1016/j.biopha.2026.119838