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To improve, itraconazole (ITA), an antifungal drug with potent anti\u2010angiogenesis activity, is co\u2010encapsulated together with PTX within the PEG\u2010PLA micelles. The strong intermolecular interactions between the payloads inhibit drug crystallization and prevent drugs from binding with external proteins, render super\u2010stable micelles upon dilution and exposure to biological environment, and enter the tumor cells through endocytosis. The co\u2010encapsulated micelles show strong anti\u2010proliferation potency against non\u2010small\u2010cell lung cancer (NSCLC) and even PTX resistant NSCLC cells in vitro and significantly improve the drug accumulation within the tumor in vivo. Compared with PTX monotherapy or combination therapy using individual PTX and ITA micelles, the co\u2010encapsulated micelle demonstrates strikingly superior efficacy in tumor growth inhibition, recurrence prevention, and reversion of PTX resistance, in Kras mutant patient derived xenografts, orthotropic models, and paclitaxel\u2010resistance subcutaneous models. Besides the pharmacokinetic improvement, therapeutic benefits are also contributed by angiogenesis inhibition and blood vessel normalization by ITA. Utilizing the pharmaceutical and pharmacological synergies between the therapeutic agents, a simple yet effective design of a combination cancer nanomedicine that is industrially scalable and clinically translatable is achieved.<\/jats:p>","DOI":"10.1002\/smll.201802112","type":"journal-article","created":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T18:21:32Z","timestamp":1542392492000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Improving Drug Delivery of Micellar Paclitaxel against Non\u2010Small Cell Lung Cancer by Coloading Itraconazole as a Micelle Stabilizer and a Tumor Vascular Manipulator"],"prefix":"10.1002","volume":"14","author":[{"given":"Ling","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, and Key Laboratory of Bioorganic Phosphorus Chemistry &amp; Chemical Biology (Ministry of Education) Tsinghua University  Beijing 100084 P. 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