title: Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif.
abstract: We have developed a dual-function drug carrier, polyethylene glycol (PEG)-derivatized farnesylthiosalicylate (FTS). Here we report that incorporation of a drug-interactive motif (Fmoc) into PEG5k-FTS2 led to further improvement in both drug loading capacity and formulation stability. Doxorubicin (DOX) formulated in PEG5k-Fmoc-FTS2 showed sustained release kinetics slower than those of DOX loaded in PEG5k-FTS2. The maximum tolerated dose of DOX- or paclitaxel (PTX)-loaded PEG5k-Fmoc-FTS2 was significantly higher than that of the free drug. Pharmacokinetics and biodistribution studies showed that DOX/PEG5k-Fmoc-FTS2 mixed micelles were able to retain DOX in the bloodstream for a significant amount of time and efficiently deliver the drug to tumor sites. More importantly, drug (DOX or PTX)-loaded PEG5k-Fmoc-FTS2 led to superior antitumor activity over other treatments including drugs formulated in PEG5k-FTS2 in breast cancer and prostate cancer models. Our improved dual function carrier with a built-in drug-interactive motif represents a simple and effective system for targeted delivery of anticancer agents.
authors.affiliation: Center for Pharmacogenetics; ‡Department of Pharmaceutical Sciences, School of Pharmacy; and §University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh, Pennsylvania 15261, United States.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.forename: Yixian
authors.initials: Y
authors.lastname: Huang
authors.forename: Wenchen
authors.initials: W
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Marquez
authors.forename: Jianqin
authors.initials: J
authors.lastname: Lu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiang
authors.initials: J
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.forename: Song
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D053769:Nanocapsules / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D053769:Nanocapsules; D011092:Polyethylene Glycols