Drug/Dye-Loaded, Multifunctional PEG鈥揅hitosan鈥揑ron Oxide Nanocomposites for Methotraxate Synergistically Self-Targeted Cancer Therapy and Dual Model Imaging

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• 作者：Jinyan Lin ; Yang Li ; Yanxiu Li ; Hongjie Wu ; Fei Yu ; Shuifan Zhou ; Liya Xie ; Fanghong Luo ; Changjian Lin ; Zhenqing Hou
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：June 10, 2015
• 年：2015
• 卷：7
• 期：22
• 页码：11908-11920
• 全文大小：744K
• ISSN：1944-8252

文摘

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 鈥渙ff鈥?in normal cells and 鈥渙n鈥?in cancer cells) and pH/intracellular protease-mediated hydrolyzing peptide bonds (able to turn drug release 鈥渙ff鈥?in systemic circulation and 鈥渙n鈥?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.