Drug/Dye-Loaded, Multifunctional PEG–Chitosan–Iron Oxide Nanocomposites for Methotraxate Synergistically Self-Targeted Cancer Therapy and Dual Model Imaging
2015
Lin, Jinyan | Li, Yang | Li, Yanxiu | Wu, Hongjie | Yu, Fei | Zhou, Shuifan | Xie, Liya | Luo, Fanghong | Lin, Changjian | Hou, Zhenqing
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.
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Эту запись предоставил National Agricultural Library