Design of an artificial natural killer cell mimicking system to target tumour cells
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| Název: | Design of an artificial natural killer cell mimicking system to target tumour cells |
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| Autoři: | Chugh, Vaishali, Kanala, Vijaya Krishna, Quandt, Dagmar, Kelly, Suainibhe, King, Damien, Jensen, Lasse, Simpson, Jeremy C., Pandit, Abhay |
| Zdroj: | Journal of Tissue Engineering. 16 |
| Témata: | NK cell membrane, gelatin microspheres, biomaterials, 3D spheroids, zebrafish xenograft breast tumour model |
| Popis: | NK cell mimics are assemblies of a cell membrane and a template that replicate biomimetic features and physicochemical properties, respectively. To develop this targeted drug delivery system, gelatin microspheres (cG) were fabricated using a water-in-oil emulsion and reinforced via DMTMM cross-linking to exhibit tunable Young's modulus, a critical parameter for cell-material interactions. These microspheres were subsequently coated with membranes derived from the human NK cell line KHYG-1 to form biomimetic NK cell mimics (cGCM), combining physicochemical control with bioinspired functionality. These engineered cGCM were non-toxic, non-inflammatory, and capable of reducing macrophage uptake by similar to 10% when incubated with differentiated THP-1 cells. In vitro studies demonstrated significant interaction/ proximity of the cGCM with cancer cells in 2D cultures of breast cancer cells (MDA-MB-231), 3D spheroids of liver (HepG2), and colon (HT-29) cancer cell models, and a zebrafish breast cancer xenograft (MDA-MB-231) model. The cGCM also evaded macrophage detection in a Kdrl:EGFP Spil:Ds Red zebrafish model. Furthermore, in a pilot assessment, loading and release of the sialyltransferase inhibitor (STI, 3Fax-Peracetyl Neu5Ac) using cGCM significantly reduced alpha-2,6 sialylation in 2D cultures of MDA-MB-231 cells, demonstrating the STI's intact functionality in inhibiting sialylation. By integrating bioinspired membranes with mechanically tunable gelatin-based carriers, our system demonstrates a multifunctional immune-mimicking platform with relevance to tissue engineering, tumour modelling, immune modulation, and drug delivery. These findings offer a promising foundation for future therapeutic strategies in cancer research and immuno-engineering. |
| Popis souboru: | electronic |
| Přístupová URL adresa: | https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-218849 https://doi.org/10.1177/20417314251349675 |
| Databáze: | SwePub |
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Nájsť tento článok vo Web of Science | Abstrakt: | NK cell mimics are assemblies of a cell membrane and a template that replicate biomimetic features and physicochemical properties, respectively. To develop this targeted drug delivery system, gelatin microspheres (cG) were fabricated using a water-in-oil emulsion and reinforced via DMTMM cross-linking to exhibit tunable Young's modulus, a critical parameter for cell-material interactions. These microspheres were subsequently coated with membranes derived from the human NK cell line KHYG-1 to form biomimetic NK cell mimics (cGCM), combining physicochemical control with bioinspired functionality. These engineered cGCM were non-toxic, non-inflammatory, and capable of reducing macrophage uptake by similar to 10% when incubated with differentiated THP-1 cells. In vitro studies demonstrated significant interaction/ proximity of the cGCM with cancer cells in 2D cultures of breast cancer cells (MDA-MB-231), 3D spheroids of liver (HepG2), and colon (HT-29) cancer cell models, and a zebrafish breast cancer xenograft (MDA-MB-231) model. The cGCM also evaded macrophage detection in a Kdrl:EGFP Spil:Ds Red zebrafish model. Furthermore, in a pilot assessment, loading and release of the sialyltransferase inhibitor (STI, 3Fax-Peracetyl Neu5Ac) using cGCM significantly reduced alpha-2,6 sialylation in 2D cultures of MDA-MB-231 cells, demonstrating the STI's intact functionality in inhibiting sialylation. By integrating bioinspired membranes with mechanically tunable gelatin-based carriers, our system demonstrates a multifunctional immune-mimicking platform with relevance to tissue engineering, tumour modelling, immune modulation, and drug delivery. These findings offer a promising foundation for future therapeutic strategies in cancer research and immuno-engineering. |
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| ISSN: | 20417314 |
| DOI: | 10.1177/20417314251349675 |