bims-livmat 2025-08-24 papers

Adv Healthc Mater. 2025 Aug 18. e01621

Bioengineering Living Biohybrid Therapeutics for Synergistic H2S Gaseous-Photothermal Cancer Eradication.

Xiaolian Deng, Yingyi Zhang, Chenyao Wu, Yuelan Liang, Jianwei Ding, Chengjie Yu, Xingding Zhang, Yiliang Lin, Jianghui Liang, Fangfang Duan, Wei Feng, Yu Chen, Xiang Gao.

Hydrogen sulfide (H2S)-mediated gaseous therapies feature high therapeutic efficacy and biosafety in cancer treatment, but conventional H2S delivery protocols suffer from poor tumor specificity and uncontrollable release. Here, a living therapeutic biohybrid is developed that integrates engineered microbes for in situ H2S production with self-mineralized copper sulfide (CuS) nanoparticles, enabling synergistic H2S gaseous-photothermal cancer treatment. These engineered facultative anaerobic bacteria Vibrio natriegens continuously produce H2S and synthesize CuS nanoparticles, forming Bac@CuS living biohybrids that inhibit the mitochondrial electron transport chain through H2S production, leading to increased reactive oxygen species production and subsequent apoptosis of cancer cells. Concurrently, Bac@CuS-mediated photothermal effect induces hyperthermia, further impairing mitochondrial function and enhancing cancer-cell death. In vivo studies demonstrate that Bac@CuS living biohybrids feature excellent biocompatibility and have achieved a 95.4% tumor inhibition rate in the breast tumor-bearing mouse model. The biohybrid therapeutic platform enables the engineered bacteria to produce non-native effectors alongside with nanoparticles, integrating synthetic biology with nanotechnology and offering a novel approach for efficient cancer eradication.

Keywords: hydrogen sulfide; living biohybrid therapeutics; living biomaterials; synergy therapy; synthetic biology

DOI: https://doi.org/10.1002/adhm.202501621

Int Forum Allergy Rhinol. 2025 Aug 18.

Engineered Microbial-Based Therapeutics Nose No Bounds: Extending Innovation to Rhinologic Disease Management.

Jonathan Pabón, Tal Danino, David A Gudis, Jonathan B Overdevest.

Advancements in synthetic biology provide an opportunity to deliver targeted and controllable precision therapy to address sinonasal diseases. By leveraging the natural microbial ecosystem of the nasal mucosa and its mutability, engineered therapeutic bacteria present a promising treatment modality currently underexplored in this field. Investigating the practical application of this emerging therapeutic option stands to enhance our management of rhinologic diseases. Synthetic biology enables us to address underlying inflammatory processes and sinonasal malignancies with bespoke microorganisms that facilitate localized microbiota modulation and immunomodulation. By harnessing the intrinsic regulatory properties of the native nasal microbiome, we can develop innovative strategies that not only improve treatment efficacy but also open new avenues for managing complex sinonasal conditions.

Keywords: engineered bacteria; microbiome; synthetic biology; therapeutic delivery

DOI: https://doi.org/10.1002/alr.23619

J Microbiol Biotechnol. 2025 Aug 15. 35 e2504042

Apoptosis-Inducing Effects of Lactobacillus plantarum DS0709 in Colorectal Cancer.

In Hwan Tae, Yunsang Kang, Jinkwon Lee, Jeongmin Lee, Jinsan Kim, Haneol Yang, Kunhyang Park, Doo-Sang Park, Dae-Soo Kim, Hyun-Soo Cho.

In colorectal cancer (CRC) treatment, various approaches, including chemotherapy (5-FU, irinotecan, and oxaliplatin), targeted therapy (VEGF inhibitor) and immunotherapy (PD-1/ PD-L1 inhibitor), are employed. However, due to side effects and limited efficacy, more effective novel therapeutic strategies have been required. In this study, we identified the anti-cancer effects of Lactobacillus plantarum DS0709, isolated from infant feces, on CRC. Treatment with the supernatant (Sup) of L. plantarum DS0709 demonstrated growth inhibition of CRC cell lines (HCT116 and SNUC5) by inducing apoptosis. Additionally, using human iPSC-derived intestinal organoids (hIO), we confirmed that L. plantarum DS0709 Sup exhibited no toxicity. Furthermore, in a 3D spheroid model mimicking in vivo conditions, L. plantarum DS0709 Sup showed similar apoptosis induction and growth-inhibitory effects as in 2D cultures. Thus, these findings suggest that L. plantarum DS0709 has the potential to be developed into a novel microbiome-based therapeutic agent for CRC, offering anti-cancer efficacy without side effects.

Keywords: L. plantarum DS0709; apoptosis; colorectal cancer

DOI: https://doi.org/10.4014/jmb.2504.04042

Cell Rep. 2025 Aug 18. pii: S2211-1247(25)00928-3. [Epub ahead of print]44(8): 116157

Gut commensal microbiota drive tailored macrophage responses.

Josh Jones, Karla Y García-Martínez, Yi-Yuan Lee, Matt Rhee, Rahul R Nath, Sola Takahashi, Benjamin Grodner, Iwijn De Vlaminck, Cynthia A Leifer, Ilana L Brito.

Macrophages serve as sentinels at the intestinal surface, responding to organismal cues to drive proinflammatory or tolerogenic responses. To date, studies of combinations of these cues do not fully capture the heterogeneity of macrophage responses. To address this gap, we performed multiplexed single-cell RNA sequencing on 74,476 human monocyte-derived macrophages following exposure to 15 bacteria, mostly commensals. We observe clusters that appeared only after macrophage exposure to bacteria, and transcriptional responses within each cluster varied by species and Gram status. The proportion of each cluster also varied among exposure conditions. Macrophages exposed to defined combinations of organisms revealed that Fusobacterium nucleatum drives inflammatory responses, whereas Mediterraneibacter gnavus tempers them. Overall, our results show that macrophages distinguish between commensal organisms, relevant to intestinal diseases characterized by altered microbiome compositions. This sequencing dataset will be a useful resource to probe human macrophage response to a broad range of bacteria.

Keywords: CP: Immunology; CP: Microbiology; TLR; bacteria; commensals; cytokine; inflammation; macrophages; microbiome; mucosal; scRNA-seq; transcriptomes

DOI: https://doi.org/10.1016/j.celrep.2025.116157

Proc Natl Acad Sci U S A. 2025 Aug 26. 122(34): e2507711122

Programmable immunoprobiotics orchestrate antitumor immune response with Pin1 inhibition for pancreatic cancer treatment.

Sichen Yuan, Xicheng Yang, Alexa M Bremmer, Yixin Wang, Sherry Li, Yu Chen, Yawen You, Quanyin Hu.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options due to its desmoplastic and immunosuppressive tumor microenvironment (TME), which impedes drug delivery and limits T cell infiltration. Immune checkpoint blockade (ICB) has shown poor efficacy in PDAC, partly due to the desmoplastic stroma and low immunogenicity. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) promotes both fibrosis and immune evasion, making it a compelling target for TME remodeling. Here, we develop a dual-action, programmable immunoprobiotic delivery system (EcN@Nbs-NP@API-1) that combines Pin1 inhibition with PD-L1 blockade to enhance immunotherapy. This system uses Escherichia coli Nissle 1917 (EcN) to selectively deliver nanoparticles encapsulating the Pin1 inhibitor API-1 to PDAC, enabling sustained release to degrade the fibrotic stroma and upregulate PD-L1 on tumor cells, promoting immune infiltration. Engineered EcN also produces anti-PD-L1 nanobodies in situ, synergizing with API-1 to boost CD8+ T cell-mediated immunity. In orthotopic PDAC mouse models, this strategy remodels the TME, enhances immune cell infiltration, and improves antitumor response while minimizing systemic toxicity. Moreover, it shows efficacy in other ECM-rich tumors, such as triple-negative breast cancer, highlighting its broader potential. This work presents a promising platform to overcome immunotherapy resistance in solid tumors.

Keywords: Pin1 inhibition; drug delivery; immune checkpoint blockade; immunoprobiotics; pancreatic ductal adenocarcinoma

DOI: https://doi.org/10.1073/pnas.2507711122