title: Hierarchical design of a polymeric nanovehicle for efficient tumor regression and imaging.
abstract: Effective delivery of therapeutics to disease sites significantly contributes to drug efficacy, toxicity and clearance. Here we designed a hierarchical polymeric nanoparticle structure for anti-cancer chemotherapy delivery by utilizing state-of-the-art polymer chemistry and co-assembly techniques. This novel structural design combines the most desired merits for drug delivery in a single particle, including a long in vivo circulation time, inhibited non-specific cell uptake, enhanced tumor cell internalization, pH-controlled drug release and simultaneous imaging. This co-assembled nanoparticle showed exceptional stability in complex biological media. Benefiting from the synergistic effects of zwitterionic and multivalent galactose polymers, drug-loaded nanoparticles were selectively internalized by cancer cells rather than normal tissue cells. In addition, the pH-responsive core retained their cargo within their polymeric coating through hydrophobic interaction and released it under slightly acidic conditions. In vivo pharmacokinetic studies in mice showed minimal uptake of nanoparticles by the mononuclear phagocyte system and excellent blood circulation half-lives of 14.4 h. As a result, tumor growth was completely inhibited and no damage was observed for normal organ tissues. This newly developed drug nanovehicle has great potential in cancer therapy, and the hierarchical design principle should provide valuable information for the development of the next generation of drug delivery systems.
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China. zhangxinge@nankai.edu.cn.
authors.forename: Jinxia
authors.initials: J
authors.lastname: An
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China. zhangxinge@nankai.edu.cn.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. sjiang@uw.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. sjiang@uw.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sinclair
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China. zhangxinge@nankai.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China. zhangxinge@nankai.edu.cn.
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. sjiang@uw.edu.
authors.forename: Kan
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. sjiang@uw.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. sjiang@uw.edu.
authors.forename: Hsiang-Chieh
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China. zhangxinge@nankai.edu.cn.
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA. sjiang@uw.edu.
authors.forename: Shaoyi
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004337:Drug Carriers; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011108:Polymers
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers