Integrated microfluidics-based construction of anti-BTN2A2 gel droplet cell preparations for non-invasive tumor-infiltrating lymphocyte therapy

Materials Today Bio, Год журнала: 2025, Номер 31, С. 101545 - 101545

Опубликована: Фев. 4, 2025

Tumor infiltrating lymphocyte therapy (TIL therapy) is one of the effective treatments for solid tumors. However, certain periods or sites tumors are not amenable to surgical resection. Meanwhile, abundant and dense extracellular matrix (ECM) regulatory cells (e.g., T (Tregs), myeloid-derived suppressor (MDSC)) in when infused back into treatment will prevent cell infiltration proliferation, thus inhibiting efficacy this approach. In study, a novel preparation was successfully developed by integrating microfluidic chip design with carbodiimide chemical modification. This surface modified BTN2A2 antibodies internally contained isolated from blood tumor hosts, along simulated collagen peptide CMP. Specifically, exerted its anti-tumor effects through multiple mechanisms: Firstly, effectively inhibited proliferation Tregs MDSCs within microenvironment; Secondly, leveraging antigen receptors (TCRs) present cells, which were similar those tumor-infiltrating lymphocytes, significantly enhanced their targeting cytotoxic capabilities; Furthermore, CMP component droplets promoted tissues. complex immunosuppressive microenvironment, synergistic action these components markedly clearance immune system. Experimental results demonstrated that cellular exhibited promising therapeutic both melanoma pancreatic cancer models. research provided platform cooperation various methods immunotherapy, holding broad application prospects.

Язык: Английский

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Microfluidic technologies for enhancing the potency, predictability and affordability of adoptive cell therapies

Nature Biomedical Engineering, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Язык: Английский

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Enhanced Intracellular Delivery via a Titanium-Coated TiO₂ Microstructure Device: Leveraging an Infrared Laser for Optimal Efficiency

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

This study presents a novel optoporation technique using titanium-coated TiO2 microstructure (TMS) device activated by an infrared diode laser for highly efficient intracellular delivery. The TMS device, fabricated with 120 nm titanium coating on dioxide (TiO2) containing microneedles (height ∼2 μm and width ∼4.5 μm), demonstrates enhanced biocompatibility thermal conductivity compared to the conventional (MS). Exposure IR (980 nm) generates heat, forming photothermal bubbles that disrupt cell membrane create transient pores biomolecular Unlike traditional methods, which rely large, vibration-sensitive lasers, laser-assisted device-based offers compact, cost-effective, portable alternative, making it suitable clinical research applications in resource-constrained environments. performance of MS devices was various cancer lines (HeLa, L929, N2a), showing superior delivery success rates biomolecules varying molecular sizes. Notably, achieved 99.30% rate smallest molecule, PI dye, 85.17% largest studied β-galactosidase enzyme-Cy5. Furthermore, consistently provided higher at lower power, minimizing cellular stress preserving survivability. Moreover, Western Blot analysis, demonstrated levels apoptosis statistically significant differences, highlighting its potential while damage. These results highlight as advanced tool large-size delivery, offering improvements stability, efficiency,

Язык: Английский

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Organ‐on‐chip for advancing CAR therapy

Clinical & Translational Immunology, Год журнала: 2025, Номер 14(2)

Опубликована: Янв. 1, 2025

Abstract Despite great strides of progress, at least 60% the responding patients relapse to CAR therapy across blood malignancies. Off‐tumor toxicity apart from functional deficits, cytopenia and infection are major unfavourable effect therapy. Models, which faithfully recapitulate physiology complexities immunocompetent tumor microenvironment (TME), paused challenges in capturing potential off‐tumor effects Importantly, a landmark change legislation allows US Food Drug Administration New Drugs Clinical Trial Rules India encourages researchers replace animal testing with cell culture approaches relevant human system. Organ‐on‐chip (OOC) based on microfluidics technology can potentially emulate multiple biochemical biophysical intricacies lymph flow microscale. Nonetheless, how evolving be enabling real‐time gene is yet realised.

Язык: Английский

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Current Advances and Future Prospects of Bulk and Microfluidic‐Enabled Electroporation Systems

Biotechnology and Bioengineering, Год журнала: 2025, Номер unknown

Опубликована: Март 5, 2025

Reversible electroporation (EP) is a pivotal biophysical technology that leverages pulsed electric fields to enhance the permeability of cell membranes, thereby facilitating introduction foreign material into cells. In this review, we provide an overview bulk electroporators and microfluidic-enabled EP systems, focusing on their controversial points mechanisms, architectures, parameter settings. Bulk have been extensively commercialized with settled form including pulse generator accessories (i.e., cuvette plates). Researchers made efforts increase throughput simplify operation systems. Additionally, microfluidics has emerged as promising for optimizing parameters enhancing performance. Given significant structural differences between these two types operating conditions such temperature, voltage, are discussed. Research tend operate single cells under more concentrated field induced by low enabling quantitative exogenous materials delivery numerical simulation. However, due cost constraints properties utilized in laboratories, commercialization laboratory prototypes impeded. Furthermore, technological limitations, current status, development trends examined.

Язык: Английский

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Advancing Allogeneic NK Cell Immunotherapy through Microfluidic Gene Delivery

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Март 7, 2025

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment, yet challenges such as manufacturing complexity, high costs, and safety concerns have spurred the development of alternatives like CAR-natural killer (NK) immunotherapies. CAR-NK therapies provide innate cytotoxicity with antigen-independent targeting, reducing risks while improving therapeutic efficacy. However, efficient genomic engineering large-scale production allogeneic NK cells remain significant obstacles. To address these challenges, a novel microfluidic gene delivery platform is developed, Y-hydroporator, designed for immunotherapy. This features Y-shaped microchannel where experience rapid hydrodynamic stretching near stagnation point, creating transient membrane discontinuities that facilitate uptake exogenous cargo. The Y-hydroporator achieves transfection efficiency, processing ≈2 × 106 min-1 maintaining long-term viability (>89%) functionality. Using this platform, human primary NKG2A-knockout are successfully generated by delivering anti-CD19 CAR mRNA CRISPR/Cas9 ribonucleoproteins, respectively. These engineered demonstrated enhanced cytotoxicity, underscoring potential transformative tool advancing cell-based

Язык: Английский

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State of the art in CAR-based therapy: In vivo CAR production as a revolution in cell-based cancer treatment

Cellular Oncology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Chimeric antigen receptor (CAR) therapy has successfully treated relapsed/refractory hematological cancers. This strategy can effectively target tumor cells. However, despite positive outcomes in clinical applications, challenges remain to overcome. These hurdles pertain the production of drugs, solid resistance, and side effects related treatment. Some cases have been missed during drug preparation due manufacturing issues, prolonged times, high costs. mainly arise from vitro process, so reevaluating this process could minimize number patients. The immune cells are traditionally collected sent laboratory; after several steps, modified express CAR gene before being injected back into patient's body. During vivo method, is introduced inside allows for treatment begin sooner, avoiding potential failures associated In review, we will elaborate on using CAR, examine benefits approach, ultimately present available solutions incorporating practice.

Язык: Английский

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Enrichment of T-lymphocytes from leukemic blood using inertial microfluidics toward improved chimeric antigen receptor-T cell manufacturing

Cytotherapy, Год журнала: 2024, Номер 26(10), С. 1264 - 1274

Опубликована: Май 10, 2024

Chimeric antigen receptor (CAR-T) cell therapy is a successful immunotherapy for treatment of blood cancers. However, hurdles in their manufacturing remain including efficient isolation and purification the T-cell starting material. Herein, we describe one-step separation based on inertial spiral microfluidics enrichment T-cells B-cell acute lymphoblastic leukemia (ALL) chronic lymphocytic (CLL) patient's samples. In healthy donors used to optimise process, lymphocyte purity was enriched from 65% (SD±0.2) 91% (SD±0.06) 45% (SD±0.1) 73% (SD±0.02). Leukemic samples had higher compared donor Efficient recovery lymphocytes achieved ALL with B-cells, monocytes leukemic blasts depleted by 80% (SD±0.09), 89% 74% (SD±0.09) respectively, 70% recovery. CLL lower numbers, process less ALL. This study demonstrates use depletion ALL, suggesting its potential address key bottleneck CAR-T workflow.

Язык: Английский

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Preparation of μ-HMX/C-Based Composite Energy Composite Microspheres by Microdroplet Technology

Langmuir, Год журнала: 2024, Номер 40(26), С. 13676 - 13687

Опубликована: Июнь 24, 2024

Taking μ-HMX particles as the main research subject, a set of microdroplet sphericalization coating technology platforms was designed and constructed to realize preparation composite microspheres by μ-HMX. The suspension stability mechanism droplet formation were investigated, application effect nanocarbon materials also analyzed. results showed that prepared sample all better spherical morphology, well good dispersibility; samples with micron-sized for had lower thermal decomposition temperature, higher energy release efficiency, mechanical sensibility, combustion performance; incorporation CNFs changed mode system, which resulted in microsphere system having safety performance. feasibility uniform spheronization when dispersed phase is low-concentration particle encapsulation process verified.

Язык: Английский

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Melanoma-associated fibroblasts in tumor-promotion flammation and antitumor immunity: novel mechanisms and potential immunotherapeutic strategies

Human Molecular Genetics, Год журнала: 2024, Номер 33(13), С. 1186 - 1193

Опубликована: Март 27, 2024

Abstract Melanoma, renowned for its aggressive behavior and resistance to conventional treatments, stands as a formidable challenge in the oncology landscape. The dynamic complex interplay between cancer cells tumor microenvironment has gained significant attention, revealing Melanoma-Associated Fibroblasts (MAFs) central players disease progression. heterogeneity of MAFs endows them with dual role melanoma. This exhaustive review seeks not only shed light on multifaceted roles orchestrating tumor-promoting inflammation but also explore their involvement antitumor immunity. By unraveling novel mechanisms underlying MAF functions, this aims provide comprehensive understanding impact melanoma development. Additionally, it delves into potential leveraging innovative immunotherapeutic strategies, offering new avenues enhancing treatment outcomes challenging realm therapeutics.

Язык: Английский

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