{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:19:29Z","timestamp":1787552369818,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n Gastric cancer (GC) is a complex disease, which may have infectious origin.\n Helicobacter pylori<\/jats:italic>\n (\n H. pylori<\/jats:italic>\n ) Gram-negative bacteria are linked with GC development. There is growing interest in nanotechnology to develop therapeutic solutions for the treatment of GC\n in situ<\/jats:italic>\n . The predictive assessment of nanomedicine efficacy in GC remains limited due to the lack of physiologically relevant models that capture tumor architecture and infection-driven reprogramming of gastric environment.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The aim of this study was to develop 3D culture of GC cell spheroids to assess the impact of selected\n H. pylori<\/jats:italic>\n components toward this microenvironment. A further goal was to develop polylactic (PLA) nanoparticles (NPs) loaded with anti-cancer drug doxorubicin (DOX) and modified with histamine (His) to improve cellular penetration of the studied NPs and test effectiveness of developed formulation in 3D spheroidal model.\n <\/jats:p>\n <\/jats:sec>\n \n Results and Disscusion<\/jats:title>\n \n It has been shown that\n H. pylori<\/jats:italic>\n components, cytotoxin associated gene A (CagA) protein and lipopolysaccharide (LPS) influenced spheroid architecture particularly by enlarging rim zone. PLA-His-DOX NPs induced cytotoxicity of spheroidal GC cells through oxidative stress amplification, DNA damage, and apoptosis. Treatment of GC spheroids with PLA-His-DOX reduced production of pro-inflammatory interleukin (IL) IL-1\u03b2 and IL-8 driven by\n H. pylori<\/jats:italic>\n soluble components, indicating a combined cytotoxic and anti-inflammatory mechanism of PLA-His-DOX.\n In vivo<\/jats:italic>\n study using\n Cavia porcellus<\/jats:italic>\n confirmed short-term tolerability of the studied unloaded carrier (PLA-His-NPs) under tested conditions with no detectable organ toxicity. In summary, 3D spheroids of AGS GC cells developed in this study\n in vitro<\/jats:italic>\n consist of predictive models that link tumor biology with infectious components and facilitate the assessment of anti-GC cell effects of PLA-His-DOX NPs. Soluble\n H. pylori<\/jats:italic>\n CagA and LPS, which\n in vivo<\/jats:italic>\n can be released from damaged bacterial cells facilitated creating controlled environment in AGS cell cultures\n in vitro<\/jats:italic>\n . However, this model did not mimic complexity of live bacterial infection. This study prompts further research for deepening the mechanisms of anti-cancer activity and efficacy of the developed PLA-His-NPs.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1935725","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T05:30:43Z","timestamp":1787549443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of 3D spheroids of AGS gastric cancer cells in vitro for exploration of H. pylori influence on tumor environment and anti-cancer activity of PLA-His-DOX nanoparticles"],"prefix":"10.3389","volume":"17","author":[{"given":"Patrycja","family":"Jaroniek","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz","place":["\u0141\u00f3d\u017a, Poland"]},{"name":"BioMedChem Doctoral School of the University of Lodz and Lodz Institutes of the Polish Academy of Sciences, University of Lodz","place":["\u0141\u00f3d\u017a, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Chmiela","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz","place":["\u0141\u00f3d\u017a, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Brzezi\u0144ski","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences","place":["\u0141\u00f3d\u017a, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Gonciarz","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz","place":["\u0141\u00f3d\u017a, Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1517\/14712598.2012.707181","article-title":"Advances in the formation, use and understanding of multi-cellular spheroids","volume":"12","author":"Achilli","year":"2012","journal-title":"Expert Opin. 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