{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:15:30Z","timestamp":1788416130042,"version":"build-2803163510"},"reference-count":29,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2015,8,8]],"date-time":"2015-08-08T00:00:00Z","timestamp":1438992000000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA174305"],"award-info":[{"award-number":["R01CA174305"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21CA173887"],"award-info":[{"award-number":["R21CA173887"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM102989"],"award-info":[{"award-number":["R01GM102989"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We have developed a dual-functional nanocarrier composed of a hydrophilic polyethylene glycol (PEG) and a hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist), which is effective in delivery of hydrophobic anticancer drug, paclitaxel (PTX). To facilitate the retention of the therapeutic activity of the carrier, FTS was coupled to PEG via a reduction-sensitive disulfide linkage (PEG5k-S-S-FTS2). PEG5k-S-S-FTS2 conjugate formed uniform micelles with very small size (\u223c30 nm) and the hydrophobic drug PTX could be readily incorporated into the micelles. Interestingly, inclusion of a disulfide linkage into the PEG5k-FTS2 micellar system resulted in a 4-fold decrease in the critical micelle concentration (CMC). In addition, the PTX loading capacity and colloidal stability of PTX-loaded micelles were improved. HPLC-MS showed that parent FTS could be more effectively released from PEG5k-S-S-FTS2 conjugate in tumor cells\/tissues compared to PEG5k-FTS2 conjugate in vitro and in vivo. PEG5k-S-S-FTS2 exhibited a higher level of cytotoxicity toward tumor cells than PEG5k-FTS2 without a disulfide linkage. Furthermore, PTX-loaded PEG5k-S-S-FTS2 micelles were more effective in inhibiting the proliferation of cultured tumor cells compared to Taxol and PTX loaded in PEG5k-FTS2 micelles. More importantly, PTX-loaded PEG5k-S-S-FTS2 micelles demonstrated superior antitumor activity compared to Taxol and PTX formulated in PEG5k-FTS2 micelles in an aggressive murine breast cancer model (4T1.2).<\/jats:p>","DOI":"10.1021\/bc500292j","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T22:38:14Z","timestamp":1407537494000},"page":"1689-1696","source":"Crossref","is-referenced-by-count":26,"title":["Reduction-Sensitive\nDual Functional Nanomicelles for\nImproved Delivery of Paclitaxel"],"prefix":"10.1021","volume":"25","author":[{"given":"Xiaolan","family":"Zhang","sequence":"first","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixian","family":"Huang","sequence":"additional","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieni","family":"Xu","sequence":"additional","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochao","family":"Ma","sequence":"additional","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Li","sequence":"additional","affiliation":[{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]},{"name":"University of Pittsburgh ;, , , ,","place":["Pittsburgh, Pennsylvania, United States, 15261"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,8,8]]},"reference":[{"key":"2026090301351766000_cit1","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1038\/491S58a","article-title":"Nanotechnology:\nCarrying drugs","volume":"491","author":"Bourzac","year":"2012","journal-title":"Nature"},{"key":"2026090301351766000_cit2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ejpb.2008.09.026","article-title":"Multifunctional\nand stimuli-sensitive pharmaceutical nanocarriers","volume":"71","author":"Torchilin","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"2026090301351766000_cit3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.4155\/tde.13.135","article-title":"Nanomicellar carriers for targeted\ndelivery of anticancer agents","volume":"5","author":"Zhang","year":"2014","journal-title":"Ther. Delivery"},{"key":"2026090301351766000_cit4","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1208\/s12248-013-9536-9","article-title":"Design and\nevaluation of a PEGylated lipopeptide equipped with drug-interactive\nmotifs as an improved drug carrier","volume":"16","author":"Zhang","year":"2014","journal-title":"AAPS J."},{"key":"2026090301351766000_cit5","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.biomaterials.2012.10.073","article-title":"PEG-derivatized\nembelin as a nanomicellar carrier for delivery of paclitaxel to breast\nand prostate cancers","volume":"34","author":"Lu","year":"2013","journal-title":"Biomaterials"},{"key":"2026090301351766000_cit6","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1021\/bc300608h","article-title":"PEG-farnesylthiosalicylate conjugate\nas a nanomicellar carrier for delivery of paclitaxel","volume":"24","author":"Zhang","year":"2013","journal-title":"Bioconjugate Chem."},{"key":"2026090301351766000_cit7","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1021\/jm00008a004","article-title":"Farnesyl derivatives of rigid carboxylic acids-inhibitors of ras-dependent\ncell growth","volume":"38","author":"Marciano","year":"1995","journal-title":"J. Med. Chem."},{"key":"2026090301351766000_cit8","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1021\/bi972032d","article-title":"Dislodgment and accelerated\ndegradation of Ras","volume":"37","author":"Haklai","year":"1998","journal-title":"Biochemistry"},{"key":"2026090301351766000_cit9","first-page":"4682","article-title":"Ras oncogenes\nin human cancer: a review","volume":"49","author":"Bos","year":"1989","journal-title":"Cancer Res."},{"key":"2026090301351766000_cit10","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1021\/jm801165r","article-title":"New derivatives\nof farnesylthiosalicylic acid (salirasib) for cancer treatment: farnesylthiosalicylamide\ninhibits tumor growth in nude mice models","volume":"52","author":"Goldberg","year":"2009","journal-title":"J.\nMed. Chem."},{"key":"2026090301351766000_cit11","doi-asserted-by":"crossref","first-page":"7486","DOI":"10.1038\/sj.onc.1204950","article-title":"Galectin-1\nbinds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation","volume":"20","author":"Paz","year":"2001","journal-title":"Oncogene"},{"key":"2026090301351766000_cit12","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0076-6879(07)00432-6","article-title":"The Ras inhibitor farnesylthiosalicylic\nacid (Salirasib) disrupts the spatiotemporal localization of active\nRas: a potential treatment for cancer","volume":"439","author":"Rotblat","year":"2008","journal-title":"Methods\nEnzymol."},{"key":"2026090301351766000_cit13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1146\/annurev-anchem-062011-143157","article-title":"Redox-responsive\ndelivery systems","volume":"5","author":"McCarley","year":"2012","journal-title":"Annu. Rev. Anal. Chem."},{"key":"2026090301351766000_cit14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0169-409X(02)00179-5","article-title":"Drug delivery\nstrategy utilizing\nconjugation via reversible disulfide linkages: role and site of cellular\nreducing activities","volume":"55","author":"Saito","year":"2003","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026090301351766000_cit15","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.biomaterials.2009.01.026","article-title":"Reduction-sensitive\npolymers and\nbioconjugates for biomedical applications","volume":"30","author":"Meng","year":"2009","journal-title":"Biomaterials"},{"key":"2026090301351766000_cit16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.colsurfb.2013.04.023","article-title":"Fabrication\nand reduction-sensitive behavior of polyion\ncomplex nano-micelles based on PEG-conjugated polymer containing disulfide\nbonds as a potential carrier of anti-tumor paclitaxel","volume":"110","author":"Huang","year":"2013","journal-title":"Colloids Surf., B: Biointerfaces"},{"key":"2026090301351766000_cit17","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/jn\/134.3.489","article-title":"Glutathione\nmetabolism and its implications for health","volume":"134","author":"Wu","year":"2004","journal-title":"J. Nutr."},{"key":"2026090301351766000_cit18","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.colsurfb.2009.12.007","article-title":"Fabrication\nof cationic\nnanomicelle from chitosan-graft-polycaprolactone as the carrier of\n7-ethyl-10-hydroxy-camptothecin","volume":"76","author":"Duan","year":"2010","journal-title":"Colloids Surf.,\nB: Biointerfaces"},{"key":"2026090301351766000_cit19","doi-asserted-by":"crossref","first-page":"6633","DOI":"10.1016\/j.biomaterials.2011.05.050","article-title":"Well-defined,\nreversible disulfide cross-linked micelles for on-demand paclitaxel\ndelivery","volume":"32","author":"Li","year":"2011","journal-title":"Biomaterials"},{"key":"2026090301351766000_cit20","doi-asserted-by":"crossref","first-page":"3706","DOI":"10.1021\/bm401086d","article-title":"Redox-responsive, core-cross-linked\nmicelles capable of on-demand, concurrent drug release and structure\ndisassembly","volume":"14","author":"Wang","year":"2013","journal-title":"Biomacromolecules"},{"key":"2026090301351766000_cit21","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/j.biomaterials.2011.11.013","article-title":"Tumor accumulation\nand antitumor efficacy of docetaxel-loaded core-shell-corona micelles\nwith shell-specific redox-responsive cross-links","volume":"33","author":"Koo","year":"2012","journal-title":"Biomaterials"},{"key":"2026090301351766000_cit22","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1021\/mp4003333","article-title":"FRET imaging\nreveals different cellular entry routes of self-assembled and disulfide\nbonded polymeric micelles","volume":"10","author":"Lee","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"2026090301351766000_cit23","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.biomaterials.2012.09.065","article-title":"Blood-stable, tumor-adaptable\ndisulfide bonded mPEG-(Cys)4-PDLLA micelles for chemotherapy","volume":"34","author":"Lee","year":"2013","journal-title":"Biomaterials"},{"key":"2026090301351766000_cit24","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1002\/adma.200800448","article-title":"PEGylated calcium phosphate\nnanocomposites as smart environment-sensitive carriers for siRNA delivery","volume":"21","author":"Zhang","year":"2009","journal-title":"Adv. Mater."},{"key":"2026090301351766000_cit25","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/nnano.2011.166","article-title":"Accumulation of sub-100\nnm polymeric micelles in poorly permeable tumours depends on size","volume":"6","author":"Cabral","year":"2011","journal-title":"Nat. Nanotechnol."},{"key":"2026090301351766000_cit26","first-page":"213","article-title":"Block copolymers\nas drug carriers","volume":"9","author":"Yokoyama","year":"1992","journal-title":"Crit. Rev. Ther. Drug Carrier\nSyst."},{"key":"2026090301351766000_cit27","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1021\/bc3000468","article-title":"PEG-derivatized\nembelin as a dual functional carrier for the delivery of paclitaxel","volume":"23","author":"Huang","year":"2012","journal-title":"Bioconjugate Chem."},{"key":"2026090301351766000_cit28","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00280-007-0451-6","article-title":"Orally administered\nFTS (salirasib) inhibits human pancreatic tumor growth in nude mice","volume":"61","author":"Haklai","year":"2008","journal-title":"Cancer Chemother. Pharmacol."},{"key":"2026090301351766000_cit29","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jchromb.2008.05.028","article-title":"Determination\nof salirasib (S-trans,trans-farnesylthiosalicylic acid) in human plasma\nusing liquid chromatography-tandem mass spectrometry","volume":"869","author":"Zhao","year":"2008","journal-title":"J. Chromatogr., B: Anal. Technol. Biomed. Life Sci."}],"container-title":["Bioconjugate\nChemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/bc500292j","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/25\/9\/1689\/7861440\/bc500292j.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bcches\/article-pdf\/25\/9\/1689\/7861440\/bc500292j.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:35:27Z","timestamp":1788413727000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bcches\/article\/25\/9\/1689\/771811\/Reduction-Sensitive-Dual-Functional-Nanomicelles"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,8]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2014,8,8]]},"published-print":{"date-parts":[[2014,9,17]]}},"URL":"https:\/\/doi.org\/10.1021\/bc500292j","relation":{},"ISSN":["1043-1802","1520-4812"],"issn-type":[{"value":"1043-1802","type":"print"},{"value":"1520-4812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,8]]}}}