title: Novel water-soluble and pH-responsive anticancer drug nanocarriers: doxorubicin-PAMAM dendrimer conjugates attached to superparamagnetic iron oxide nanoparticles (IONPs).
abstract: PH-responsive drug release system based on the conjugates of PAMAM dendrimers-doxorubicin (PAMAM-DOX) and superparamagnetic iron oxide (Fe(3)O(4)) nanoparticles (IONPs) has been constructed and characterized. The IONPs were stabilized by mPEG-G2.5 PAMAM dendrimers. The anticancer drug DOX was conjugated to the dendrimer segments of amino-stabilized IONPs using hydrazine as the linker via hydrazone bonds, which is acid cleavable and can be used as an ideal pH-responsive drug release system. The drug release profiles of DOX-PAMAM dendrimer conjugates were studied at pH 5.0 and 7.4. The results showed that the hydrolytic release profile can be obtained only at the condition of lysosomal pH (pH=5.0), and IONPs participated in carrying DOX to the tumor by the Enhanced Permeability and Retention (EPR) effect. These novel DOX-conjugated IONPs have the potential to enhance the effect of MRI contrast and cancer therapy in the course of delivering anticancer drugs to their target sites. Although the dendrimer-DOX-coated IONPs do not have any targeting ligands attached on their surface, they are potentially useful for cancer diagnosis in vivo.
authors.affiliation: Department of Chemistry, Alan G. MacDiarmid Institute of Jilin University, Changchun 130023, China.
authors.forename: Yulei
authors.initials: Y
authors.lastname: Chang
authors.forename: Xinlei
authors.initials: X
authors.lastname: Meng
authors.forename: Yili
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.forename: Bao
authors.initials: B
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Zhu
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Li
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000175:diagnosis*; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D003287:Contrast Media; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D014867:Water; D004317:Doxorubicin