title: Drug/Dye-Loaded, Multifunctional PEG-Chitosan-Iron Oxide Nanocomposites for Methotraxate Synergistically Self-Targeted Cancer Therapy and Dual Model Imaging.
abstract: Multifunctional nanocomposites hold great potential to integrate therapeutic and diagnostic functions into a single nanoscale structure. In this paper, we prepared the MTX-PEG-CS-IONPs-Cy5.5 nanocomposites by functionalizing the surface of chitosan-decorated iron oxide nanoparticles (CS-IONPs) with polyethylene glycolated methotraxate (MTX-PEG) and near-infrared fluorescent cyanin dye (Cy5.5). A clinically useful PEGylated anticancer prodrug, MTX-PEG, was also developed as a tumor cell-specific targeting ligand for self-targeted cancer treatment. In such nanocomposites, the advantage was that the orthogonally functionalized, self-targeted MTX-PEG-CS-IONPs-Cy5.5 can synergistically combine an early phase selective tumor-targeting efficacy with a late-phase cancer-killing effect, which was also confirmed by dual model (magnetic resonance and fluorescence) imaging. Furthermore, with the aids of the folate (FA) receptor-mediated endocytosis (able to turn cellular uptake "off" in normal cells and "on" in cancer cells) and pH/intracellular protease-mediated hydrolyzing peptide bonds (able to turn drug release "off" in systemic circulation and "on" inside endo/lysosomes), the MTX-PEG-CS-IONPs-Cy5.5 could deliver MTX to FA receptors-overexpressed cancer cells, showing the improved anticancer activity with the reduced side effects. Together, the MTX-PEG-CS-IONPs-Cy5.5 could act as a highly convergent, flexible, and simplified system for dual model imaging and synergistically self-targeted cancer therapy, holding great promise for versatile biomedical applications in future.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Lin
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yanxiu
authors.initials: Y
authors.lastname: Li
authors.affiliation: §Department of Pharmacy, School of Pharmaceutical Science, Xiamen University, Xiamen 361102, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Shuifan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: ⊥The First Affiliated Hospital of Xiamen University, Xiamen 361002, China.
authors.forename: Liya
authors.initials: L
authors.lastname: Xie
authors.affiliation: ∥Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Luo
authors.forename: Changjian
authors.initials: C
authors.lastname: Lin
authors.affiliation: ◊Department of Physics, Changji University, Changji 831100, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Hou
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry / Q000627:therapeutic use; D003952:Diagnostic Imaging; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008727:Methotrexate / Q000737:chemistry / Q000627:therapeutic use; D053761:Nanocomposites / Q000737:chemistry* / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide; D011092:Polyethylene Glycols; D048271:Chitosan; D008727:Methotrexate
keywords: MTX-PEG; drug delivery; magnetic resonance imaging; self-targeted cancer therapy