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Also, the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing the therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti\u2010CSC agent thioridazine (THZ), and the PD\u20101\/PD\u2010L1 inhibitor HY19991 (HY) are all incorporated into an enzyme\/pH dual\u2010sensitive nanoparticle with a micelle\u2013liposome double\u2010layer structure. The particle size shrinks when the nanoparticle transfers from circulation to tumor tissues, favoring both pharmacokinetics and cellular uptake, meanwhile achieving sequential drug release where needed. This nano device, named PM@THL, increases the intratumoral drug concentrations in mice and exhibits significant anticancer efficacy, with tumor inhibiting rate of 93.45% and lung metastasis suppression rate of 97.64%. It also reduces the proportion of CSC and enhances the T cells infiltration in tumor tissues, and thus prolongs the survival of mice. The cocktail therapy based on the spatio\u2010temporally controlled nano device will be a promising strategy for treating breast cancer.<\/jats:p>","DOI":"10.1002\/adma.201806202","type":"journal-article","created":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T09:27:48Z","timestamp":1544002068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Cocktail Strategy Based on Spatio\u2010Temporally Controlled Nano Device Improves Therapy of Breast Cancer"],"prefix":"10.1002","volume":"31","author":[{"given":"Tianqun","family":"Lang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Drug Research &amp; Center of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences  501 Haike Road Shanghai 201203 China"},{"name":"School of Pharmacy University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research &amp; 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