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This study investigated TIPE1's role in regulating autophagy and PTX sensitivity and developed ROS\u2010responsive TIPE1 mRNA\u2010loaded nanoparticles (TIPE1m NPs) as a therapeutic strategy. PTX\u2010resistant TNBC cell lines were established, and integrated transcriptomic and proteomic analyses were performed. TIPE1 was downregulated in resistant cells, while higher TNFAIP8L1 expression in public breast cancer cohorts was associated with better survival and improved PTX response. Mechanistically, TIPE1 overexpression was associated with ubiquitination\u2010related reduction in the stability of the small GTPase RAB7A, leading to impaired autophagic flux, increased ROS accumulation, and enhanced PTX\u2010induced apoptosis. Conversely, TIPE1 knockdown stabilized RAB7A, enhanced autophagy, and increased PTX tolerance. ROS\u2010responsive TIPE1m NPs were constructed to restore TIPE1 expression in resistant cells. TIPE1m NPs suppressed autophagy, increased ROS, and enhanced PTX\u2010induced apoptosis in vitro. In PTX\u2010resistant xenografts, combined TIPE1m NPs and PTX treatment suppressed tumor growth without obvious systemic toxicity. These findings identify the TIPE1\u2013RAB7A\u2013autophagy axis as a potential therapeutic target and support TIPE1 mRNA delivery as a strategy to overcome PTX resistance in TNBC.<\/jats:p>","DOI":"10.1002\/advs.76975","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:51:28Z","timestamp":1786009888000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nanoparticle\u2010Mediated TIPE1 mRNA Delivery Enhances Paclitaxel Sensitivity in Triple\u2010Negative Breast Cancer by Modulating RAB7A Ubiquitination\u2010Associated Stability and Autophagy"],"prefix":"10.1002","author":[{"given":"Wei","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Breast Surgery Zibo Central Hospital Affiliated to Binzhou Medical University  Zibo 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