{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:19:40Z","timestamp":1791994780297,"version":"4.4.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"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. Oncol."],"abstract":"<jats:sec><jats:title>Background\/Objectives<\/jats:title><jats:p>Breast cancer treatment remains challenged by the non-specific distribution and systemic toxicity of conventional chemotherapeutics. Celastrol (CEL), a natural compound with antitumor efficacy, faces clinical limitations due to its toxicity and poor solubility. Glycyrrhizic acid (GA), known for tumor-suppressive and membrane-modifying properties, offers potential to enhance targeted drug delivery. This study aimed to develop GA-modified liposomes (GA\/LIP-CEL) to synergistically improve CEL\u2019s therapeutic specificity and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GA\/LIP-CEL nanoparticles were engineered via thin-film hydration, replacing cholesterol with GA. Physicochemical properties were characterized using TEM, DLS, and HPLC. <jats:italic>In vitro<\/jats:italic> evaluations included stability assays, cellular uptake (flow cytometry), cytotoxicity (MTT assay), mitochondrial membrane potential (JC-1 staining), apoptosis (Annexin V\/PI), DNA damage (\u03b3-H2AX immunofluorescence), and cell cycle analysis in BT549 breast cancer and MCF-10A normal cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GA\/LIP-CEL exhibited uniform spherical morphology (122.48 \u00b1 5.37 nm), high drug loading (87.75 \u00b1 2.61%), sustained release (70.13% cumulative release at 24\u00a0h), and colloidal stability (negligible size variation over 14 days). Compared to LIP-CEL, GA\/LIP-CEL reduced IC50 in BT549 cells while lowering cytotoxicity in MCF-10A cells. Compared with the LIP-CEL group, GA\/LIP-CEL treatment demonstrated a statistically significant increase in apoptotic cell proportion (P &amp;lt; 0.05). Enhanced mitochondrial dysfunction (P &amp;lt; 0.05) and DNA (P &amp;lt; 0.05) damage were observed. GA modification improved cellular uptake potentially via regulating membrane fluidity and receptor-mediated endocytosis effects, and induced S-phase arrest (31.66 \u00b1 1.70% cells).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GA\/LIP-CEL combines GA\u2019s membrane-targeting capabilities with CEL\u2019s therapeutic effects, improving stability, specificity, and safety. This platform represents a novel strategy for precision drug delivery, addressing limitations of conventional systems through natural component integration. Further validation of <jats:italic>in vivo<\/jats:italic> performance and pharmacokinetics is warranted to advance clinical translation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1602585","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T09:54:29Z","timestamp":1747734869000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Engineered celastrol liposomes with glycyrrhizic acid augment synergistic antitumor efficacy in breast 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