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However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian and pancreatic cancer, which regularly employ regimens of intravenous and\/or intraperitoneal chemotherapy (e.g., gemcitabine, cisplatin, pemetrexed and paclitaxel) with limited results. Here, we show that a \u201ctwo-step\u201d nanoparticle (NP) delivery system may address this limitation. This two-step approach involves the<jats:italic>separate<\/jats:italic>administration of NP and drug where, first, the NP localizes to tumor. Second, subsequent administration of drug then rapidly concentrates into the NP already stationed within the target tissue. This two-step method results in a greater than 5-fold increase in intratumoral drug concentrations compared to conventional \u201cdrug-alone\u201d administration. These results suggest that this unique two-step delivery may provide a novel method for increasing drug concentrations in target tissues.<\/jats:p>","DOI":"10.1038\/srep18720","type":"journal-article","created":{"date-parts":[[2016,1,7]],"date-time":"2016-01-07T10:27:38Z","timestamp":1452162458000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles"],"prefix":"10.1038","volume":"6","author":[{"given":"Aaron H.","family":"Colby","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan D.","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert F.","family":"Padera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolonda L.","family":"Colson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W.","family":"Grinstaff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,7]]},"reference":[{"key":"BFsrep18720_CR1","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1002\/smll.201100442","volume":"7","author":"J Wang","year":"2011","unstructured":"Wang, J., Byrne, J. 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