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Herein, a LyP\u20101 and chondroitin sulfate (CS) dual\u2010modified liposome co\u2010loaded with paclitaxel (PTX) and cryptotanshinone (CTS), namely CS\/LyP\u20101\u2010PC Lip, is engineered for TNBC chemoimmunotherapy via induction of immunogenic cell death (ICD) and inhibition of signal transducer and activator of transcript\u20103 (STAT3) activation. CS\/LyP\u20101\u2010PC Lip enhances cellular uptake through p32 and CD44 dual receptor\u2010mediated endocytosis. Within the tumor, the CS layer is continuously detached by hyaluronidase to release drugs. Subsequently, CTS sensitizes the cytotoxicity of PTX to 4T1 tumor cells. PTX induces ICD of tumor cells and facilitates infiltration of cytotoxic T lymphocyte to provoke immune response. Meanwhile, the concomitant delivery of CTS inhibits STAT3 activation to decrease infiltration of regulatory T cell, M2\u2010type tumor\u2010associated macrophage, and myeloid\u2010derived suppressor cell, thus reversing ITM. Markedly, the dual\u2010targeting liposome shows superior anti\u2010tumor efficacy in subcutaneous TNBC mice and significant lung metastasis suppression in tumor metastasis model. Overall, this work offers a feasible combination regimen and a promising nanoplatform for the development of TNBC chemoimmunotherapy.<\/jats:p>","DOI":"10.1002\/smll.202302834","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T12:41:31Z","timestamp":1685709691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Dual\u2010Targeting Liposome Enhances Triple\u2010Negative Breast Cancer Chemoimmunotherapy through Inducing Immunogenic Cell Death and Inhibiting STAT3 Activation"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5890-7698","authenticated-orcid":false,"given":"Kaipei","family":"Luo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu 611137 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