title: Validation of a Janus role of methotrexate-based PEGylated chitosan nanoparticles in vitro.
abstract: 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.
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China ; Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China ; Cancer Research Center, Medical College, Xiamen University, Xiamen 361005, China.
authors.forename: Fanghong
authors.initials: F
authors.lastname: Luo
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China ; Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cui
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361002, China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China ; Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biomaterials and Research Center of Biochemical Engineering, College of Materials, Xiamen University, Xiamen 361005, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.
authors.forename: Qiqing
authors.initials: Q
authors.lastname: Zhang
keywords: Chitosan; Drug delivery system; Methotrexate; Nanoparticles; Tumor
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