title: Multifunctional SPIO/DOX-loaded wormlike polymer vesicles for cancer therapy and MR imaging.
abstract: Stable and tumor-targeting multifunctional wormlike polymer vesicles simultaneously loaded with superparamagnetic iron oxide (SPIO) nanoparticles (NPs) as magnetic resonance imaging (MRI) contrast agent and anticancer drug doxorubicin (DOX) were developed for targeted cancer therapy and ultrasensitive MR imaging. These multifunctional wormlike polymer vesicles were formed by heterobifunctional amphiphilic triblock copolymers R (R = methoxy or folate (FA))-PEG(114)-PLA(x)-PEG(46)-acrylate using a double emulsion method. The long PEG segments bearing methoxy/folate groups (CH(3)O/FA-PEG(114)) were mostly segregated to the outer hydrophilic PEG layers of the wormlike vesicles thereby providing active tumor-targeting ability, while the short PEG segments bearing acrylate groups (PEG(46)-acrylate) were mostly segregated onto the inner hydrophilic PEG layers of the wormlike vesicles thereby allowing the inner PEG layers to be crosslinked via free radical polymerization for enhanced in vivo stability. The hydrophobic anticancer drug, DOX, was loaded into the hydrophobic membrane of the wormlike vesicles. Meanwhile, a cluster of hydrophilic SPIO NPs was encapsulated into the aqueous cores of the stable wormlike vesicles with crosslinked inner PEG layers for ultrasensitive MRI detection. Cellular uptake of the FA-conjugated wormlike vesicles facilitated by the folate receptor-mediated endocytosis process was higher than that of the FA-free vesicles thereby leading to high cytotoxicity against the HeLa human cervical tumor cell line. Moreover, the SPIO/DOX-loaded wormlike vesicles with crosslinked inner PEG layers demonstrated a much higher r(2) relaxivity value than Feridex, a commercially available T(2) agent, which can be attributed to the high SPIO NPs loading level as well as the SPIO clustering effect. These unique stable and tumor-targeting multifunctional SPIO/DOX-loaded wormlike polymer vesicles would make targeted cancer theranostics possible thereby paving the road for personalized medicine.
authors.affiliation: Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Yang
authors.forename: Jamison J
authors.initials: JJ
authors.lastname: Grailer
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Rowland
authors.forename: Alireza
authors.initials: A
authors.lastname: Javadi
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Hurley
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Steeber
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
mesh_terms: D016923:Cell Death / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry*; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D005492:Folic Acid / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003911:Dextrans; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D011108:Polymers; D004317:Doxorubicin; D005492:Folic Acid; C065507:ferumoxides