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Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro

Fanghong Luo124, Yang Li12, Mengmeng Jia2, Fei Cui2, Hongjie Wu3, Fei Yu1, Jinyan Lin12, Xiangrui Yang2, Zhenqing Hou2* and Qiqing Zhang5*

Author Affiliations

1 Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China

2 Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China

3 Department of Pharmacy, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361002, China

4 Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China

5 Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China

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Nanoscale Research Letters 2014, 9:363  doi:10.1186/1556-276X-9-363

Published: 23 July 2014


Recently, methotrexate (MTX) has been used to target to folate (FA) receptor-overexpressing cancer cells for targeted drug delivery. However, the systematic evaluation of MTX as a Janus-like agent has not been reported before. Here, we explored the validity of using MTX playing an early-phase cancer-specific targeting ligand cooperated with a late-phase therapeutic anticancer agent based on the PEGylated chitosan (CS) nanoparticles (NPs) as drug carriers. Some advantages of these nanoscaled drug delivery systems are as follows: (1) the NPs can ensure minimal premature release of MTX at off-target site to reduce the side effects to normal tissue; (2) MTX can function as a targeting ligand at target site prior to cellular uptake; and (3) once internalized by the target cell, the NPs can function as a prodrug formulation, releasing biologically active MTX inside the cells. The (MTX + PEG)-CS-NPs presented a sustained/proteases-mediated drug release. More importantly, compared with the PEG-CS-NPs and (FA + PEG)-CS-NPs, the (MTX + PEG)-CS-NPs showed a greater cellular uptake. Furthermore, the (MTX + PEG)-CS-NPs demonstrated a superior cytotoxicity compare to the free MTX. Our findings therefore validated that the MTX-loaded PEGylated CS-NPs can simultaneously target and treat FA receptor-overexpressing cancer cells.

Methotrexate; Chitosan; Drug delivery system; Tumor; Nanoparticles