bims-livmat 2025-04-20 papers

Adv Drug Deliv Rev. 2025 Apr 16. pii: S0169-409X(25)00062-6. [Epub ahead of print] 115577

Paving the way for bacteria-based drug delivery: biohybrid microrobots emerging from microrobotics and synthetic biology.

Elena Totter, Emilie von Einsiedel, Lisa Regazzoni, Simone Schuerle.

Advances in microrobotics and synthetic biology are paving the way for innovative solutions to long-standing challenges in drug delivery. Both fields have independently worked on engineering bacteria as a therapeutic system, focusing on enhancing propulsion, cargo delivery, detection, and biocompatibility. Bacteria, with their inherent adaptability and functional versatility, serve as an ideal foundation for these efforts, enabling them to navigate complex biological environments such as the human body. This review explores the convergence of microrobotics and synthetic biology, which has catalysed the development of biohybrid bacterial microrobots that integrate the strengths of both disciplines. By incorporating external control modalities - such as light, ultrasound, and magnetic fields - these hybrid systems address the limitations of purely microrobotic or biological approaches, offering new opportunities to enhance precision and efficacy in targeted therapies. However, realising the full potential of biohybrid bacterial microrobots requires overcoming critical challenges, such as ensuring compatibility between biological and synthetic components, scaling manufacturing processes, and defining regulatory pathways tailored to living therapeutics. Addressing these hurdles through joint, interdisciplinary research efforts, can unlock the transformative possibilities of these systems in modern medicine.

Keywords: Bacteria-based microrobots; Biohybrid systems; Microrobotics; Synthetic microbiology; Targeted drug delivery

DOI: https://doi.org/10.1016/j.addr.2025.115577

Adv Drug Deliv Rev. 2025 Apr 12. pii: S0169-409X(25)00064-X. [Epub ahead of print] 115579

Designing live bacterial therapeutics for cancer.

Jaehyun Lee, Sandra McClure, Ralph R Weichselbaum, Mark Mimee.

Humans are home to a diverse community of bacteria, many of which form symbiotic relationships with their host. Notably, tumors can also harbor their own unique bacterial populations that can influence tumor growth and progression. These bacteria, which selectively colonize hypoxic and acidic tumor microenvironments, present a novel therapeutic strategy to combat cancer. Advancements in synthetic biology enable us to safely and efficiently program therapeutic drugs production in bacteria, further enhancing their potential. This review provides a comprehensive guide to utilizing bacteria for cancer treatment. We discuss key considerations for selecting bacterial strains, emphasizing their colonization efficiency, the delicate balance between safety and anti-tumor efficacy, and the availability of tools for genetic engineering. We also delve into strategies for precise spatiotemporal control of drug delivery to minimize adverse effects and maximize therapeutic impact, exploring recent examples of engineered bacteria designed to combat tumors. Finally, we address the underlying challenges and future prospects of bacterial cancer therapy. This review underscores the versatility of bacterial therapies and outlines strategies to fully harness their potential in the fight against cancer.

Keywords: Bacterial drug delivery; Bacterial therapeutics; Cancer therapy; Engineered bacteria; Synthetic biology

DOI: https://doi.org/10.1016/j.addr.2025.115579

Adv Drug Deliv Rev. 2025 Apr 11. pii: S0169-409X(25)00063-8. [Epub ahead of print]221 115578

Be a GEM: Biocontained, environmentally applied, genetically engineered microbes.

Tae Seok Moon.

Technological advances in engineering biology or synthetic biology have enabled practical applications of genetically engineered microbes (GEMs), including their use as living diagnostics and vehicles for therapeutics. However, technological and non-technological issues associated with biocontainment of GEMs have yet to be addressed before fully realizing their potential. In this short perspective, I briefly discuss the relevant technologies for GEM biocontainment as well as environmental impacts, regulatory issues, and public perception of GEMs.

Keywords: Biocontainment; GMO regulation; Genetic circuit; Genetically engineered microbe; Genetically modified organism; Probiotic; Public perception

DOI: https://doi.org/10.1016/j.addr.2025.115578

Cancers (Basel). 2025 Apr 07. pii: 1252. [Epub ahead of print]17(7):

Optimizing Cancer Treatment Through Gut Microbiome Modulation.

Kyuri Kim, Mingyu Lee, Yoojin Shin, Yoonji Lee, Tae-Jung Kim.

The gut microbiome plays a pivotal role in modulating cancer therapies, including immunotherapy and chemotherapy. Emerging evidence demonstrates its influence on treatment efficacy, immune response, and resistance mechanisms. Specific microbial taxa enhance immune checkpoint inhibitor efficacy, while dysbiosis can contribute to adverse outcomes. Chemotherapy effectiveness is also influenced by microbiome composition, with engineered probiotics and prebiotics offering promising strategies to enhance drug delivery and reduce toxicity. Moreover, microbial metabolites, such as short-chain fatty acids, and engineered microbial systems have shown potential to improve therapeutic responses. These findings underscore the importance of personalized microbiome-based approaches in optimizing cancer treatments.

Keywords: cancer; chemotherapy; immunotherapy; microbial metabolite; microbiome; prebiotics; probiotics

DOI: https://doi.org/10.3390/cancers17071252

Adv Drug Deliv Rev. 2025 Apr 16. pii: S0169-409X(25)00076-6. [Epub ahead of print] 115591

Enhancing the persistence of engineered biotherapeutics in the gut: Adhesion, glycan metabolism, and environmental resistance.

Yujin Lee, Hyun Gi Koh, Kyoung Heon Kim, Yong-Su Jin, Bong Hyun Sung, Jungyeon Kim.

Engineered live biotherapeutic products (eLBPs) are receiving increasing attention as next-generation therapeutics to treat a variety of diseases with high specificity and effectiveness. Despite their potential, eLBPs face challenges, such as limited colonization, competition with native microbiota, nutrient depletion, and susceptibility to gastrointestinal stresses, which ultimately reduce their persistence in the gut and hinder their therapeutic efficacy. This review examines the key strategies to enhance the persistence and activity of eLBPs in the gut environment. First, methods to strengthen the adhesion capacity of eLBPs are discussed, including genetic engineering to express adhesins and chemical surface modifications to improve their binding to mucus and epithelial cells. Second, strategies to improve the ability of eLBPs to efficiently use mucin-derived sugars, which are continuously secreted by intestinal epithelial cells, were highlighted. These strategies involve the introduction and optimization of glycan-degrading enzymes and metabolic pathways for key mucin sugars, such as N-acetylglucosamine, galactose, and sialic acid, to support sustained energy production and enhance gut colonization. Third, strategies to improve the resistance of eLBPs against environmental stress are discussed, including genetic modifications to stabilize cell membranes, enhancement of ion pump activity, overexpression of stress-response proteins, and encapsulation techniques to provide protection. The implementation of these strategies can address challenges related to gut colonization by eLBPs, thereby enhancing their metabolic activity and enabling sustained and efficient secretion of therapeutic molecules. This review offers a comprehensive framework for developing and optimizing eLBPs, paving the way for their successful clinical application with enhanced effectiveness in treating gastrointestinal and systemic diseases.

Keywords: Adhesion capacity; Engineered live biotherapeutic products; Environmental stress resistance; Gut colonization; Mucin-derived sugars

DOI: https://doi.org/10.1016/j.addr.2025.115591

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2025 Mar-Apr;17(2):17(2): e70011

Bacterial Autonomous Intelligent Microrobots for Biomedical Applications.

Haotian Chen, Yingze Li, Zhenguang Li, Yuantai Sun, Weicheng Gu, Chang Chen, Yu Cheng.

Micro/nanorobots are being increasingly utilized as new diagnostic and therapeutic platforms in the biomedical field, enabling remote navigation to hard-to-reach tissues and the execution of various medical procedures. Although significant progress has been made in the development of biomedical micro/nanorobots, how to achieve closed-loop control of them from sensing, memory, and precise trajectory planning to feedback to carry out biomedical tasks remains a challenge. Bacteria with self-propulsion and autonomous intelligence properties are well suited to be engineered as microrobots to achieve closed-loop control for biomedical applications. By virtue of synthetic biology, bacterial microrobots possess an expanded genetic toolbox, allowing them to load input sensors to respond or remember external signals. To achieve accurate control in the complex physiological environment, the development of bacterial microrobots should be matched with the corresponding control system design. In this review, a detailed summary of the sensing and control mechanisms of bacterial microrobots is presented. The engineering and applications of bacterial microrobots in the biomedical field are highlighted. Their future directions of bacterial autonomous intelligent microrobots for precision medicine are forecasted.

Keywords: autonomous intelligence; bacteria; biomedical applications; microrobots; synthetic biology

DOI: https://doi.org/10.1002/wnan.70011