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: Fanghong Luo, Yang Li, Mengmeng Jia, Fei Cui, Hongjie Wu, Fei Yu, Jinyan Lin, Xiangrui Yang, Zhenqing Hou, Qiqing Zhang
• Journal: Nanoscale research letters (Nanoscale Res Lett) Vol. 9 Issue 1 Pg. 363 ( 2014) ISSN: 1931-7573 [Print] United States
• PMID: 25114653 (Publication Type: Journal Article)