期刊
ACS APPLIED MATERIALS & INTERFACES
卷 7, 期 22, 页码 11908-11920出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.5b01685
关键词
MTX-PEG; magnetic resonance imaging; drug delivery; self-targeted cancer therapy
资金
- National Natural Science Foundation of China [31271071, 81000660]
- Fujian Province Medical Innovation Project [2014-CXB-350]
- Army Logistics Scientific Research Project [CNJ14C007]
- Natural Science Foundation of Fujian Province of China [2013J01384]
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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