Biofilm Potentiates Cancer‐Promoting Effects of Tumor‐Associated Macrophages in a 3D Multi‐Faceted Tumor Model

Deng, Yanlin; Fu, Yatian; Chua, Song Lin; Khoo, Bee Luan

doi:10.1002/smll.202205904

Cited by 7 publications

(1 citation statement)

References 91 publications

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“…By combining microfluidics and deep learning, the system achieved a high throughput of approximately 25,000 cells per minute, allowing for high sensitivity, low cost, and ease of operation. In the future, the cDC + ATMQcD system is expected to find wide applications, including liquid biopsy, drug testing, and investigation of disease mechanisms, by integrating with microfluidics for biomarker enrichment 46 , 47 and in-vitro disease models 48 , 49 .…”

Section: Discussionmentioning

confidence: 99%

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

Hua,

Zou,

et al. 2023

Microsyst Nanoeng

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Cellular deformability is a promising biomarker for evaluating the physiological state of cells in medical applications. Microfluidics has emerged as a powerful technique for measuring cellular deformability. However, existing microfluidic-based assays for measuring cellular deformability rely heavily on image analysis, which can limit their scalability for high-throughput applications. Here, we develop a parallel constriction-based microfluidic flow cytometry device and an integrated computational framework (ATMQcD). The ATMQcD framework includes automatic training set generation, multiple object tracking, segmentation, and cellular deformability quantification. The system was validated using cancer cell lines of varying metastatic potential, achieving a classification accuracy of 92.4% for invasiveness assessment and stratifying cancer cells before and after hypoxia treatment. The ATMQcD system also demonstrated excellent performance in distinguishing cancer cells from leukocytes (accuracy = 89.5%). We developed a mechanical model based on power-law rheology to quantify stiffness, which was fitted with measured data directly. The model evaluated metastatic potentials for multiple cancer types and mixed cell populations, even under real-world clinical conditions. Our study presents a highly robust and transferable computational framework for multiobject tracking and deformation measurement tasks in microfluidics. We believe that this platform has the potential to pave the way for high-throughput analysis in clinical applications, providing a powerful tool for evaluating cellular deformability and assessing the physiological state of cells.

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Section: Discussionmentioning

confidence: 99%

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

Hua,

Zou,

et al. 2023

Microsyst Nanoeng

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Bacterial Iron Siderophore Drives Tumor Survival and Ferroptosis Resistance in a Biofilm‐Tumor Spheroid Coculture Model

Yeung,

Ma,

Deng

et al. 2024

Advanced Science

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Interactions between tumoral cells and tumor‐associated bacteria within the tumor microenvironment play a significant role in tumor survival and progression, potentially impacting cancer treatment outcomes. In lung cancer patients, the Gram‐negative pathogen Pseudomonas aeruginosa raises questions about its role in tumor survival. Here, a microfluidic‐based 3D‐human lung tumor spheroid‐P. aeruginosa model is developed to study the bacteria's impact on tumor survival. P. aeruginosa forms a tumor‐associated biofilm by producing Psl exopolysaccharide and secreting iron‐scavenging pyoverdine, which is critical for establishing a bacterial community in tumors. Consequently, pyoverdine promotes cancer progression by reducing susceptibility to iron‐induced death (ferroptosis), enhancing cell viability, and facilitating several cancer hallmarks, including epithelial–mesenchymal transition and metastasis. A promising combinatorial therapy approach using antimicrobial tobramycin, ferroptosis‐inducing thiostrepton, and anti‐cancer doxorubicin could eradicate biofilms and tumors. This work unveils a novel phenomenon of cross‐kingdom cooperation, where bacteria protect tumors from death, and it paves the way for future research in developing antibiofilm cancer therapies. Understanding these interactions offers potential new strategies for combatting cancer and enhancing treatment efficacy.

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Engineered Macrophages Tune Intratumoral Cytokines through Precisely Controlled Self‐Pyroptosis to Enhance Bladder Cancer Immunotherapy

Guo,

Dai,

Yang

et al. 2023

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Engineered macrophages are a promising tool for drug delivery and immunotherapy in cancer treatment. However, simultaneous targeted enrichment and controllable immunological activation of these macrophages at the tumor site remains challenging. As a solution, macrophages loaded with an advanced nanoparticle encapsulating CpG‐conjugated magnetic nanoclusters (MNC) with indocyanine green (ICG) and nigericin (NIG) (MNC‐ICG‐NIG@SiO2 (MINS)), utilizing Se─Se bond‐modified SiO2, are designed and applied in bladder cancer, which is typically managed surgically, followed by Bacillus Calmette–Guerin (BCG) adjuvant instillation therapy. Upon intravenous administration, BCG‐mediated tumor‐localized inflammation leads to targeted accumulation of MINS@MΦ. MINS@MΦ accumulates within the tumor tissue and is immunologically activated through laser irradiation, leading to ICG‐mediated generation of reactive oxygen species, Se─Se bond cleavage, and subsequent NIG release to induce self‐pyroptosis. Consequently, MINS@MΦ releases Fe2+ ions and CpG, thus promoting the M1 polarization of tumor‐associated macrophages and secretion of appropriate antitumor cytokines. However, without intervention, MINS@MΦ undergoes apoptosis in the bloodstream after 48 h without eliciting any immune response. Therefore, this innovative approach optimizes and enhances the efficacy of BCG immunotherapy by precisely modulating the cytokines for effective bladder cancer treatment without inducing a systemic inflammatory response.

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Biofilm Potentiates Cancer‐Promoting Effects of Tumor‐Associated Macrophages in a 3D Multi‐Faceted Tumor Model

Cited by 7 publications

References 91 publications

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

A deformability-based biochip for precise label-free stratification of metastatic subtypes using deep learning

Bacterial Iron Siderophore Drives Tumor Survival and Ferroptosis Resistance in a Biofilm‐Tumor Spheroid Coculture Model

Engineered Macrophages Tune Intratumoral Cytokines through Precisely Controlled Self‐Pyroptosis to Enhance Bladder Cancer Immunotherapy

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