Highly Water-Soluble Methotrexate-Polyethyleneglycol-Rhodamine Prodrug Micelle for High Tumor Inhibition Activity.

Highly water-soluble prodrug micelle (50-fold compared with free MTX) of methotrexate-polyethyleneglycol-rhodamine (MTX-PEG-rhodamine) and MTX-mPEG was synthesized by the esterification reaction. The stability of the prodrug micelles was evaluated in phosphate buffer saline (PBS) with 10% fetal bovine serum (FBS). The tumor volume of the saline, MTX, and MTX-PEG-rhodamine groups was increased 3.7-fold, 2.8-fold, and 1.8-fold, respectively, compared with the initial tumor volume. TUNEL and drug distribution results further confirmed that the micelle of MTX-PEG-rhodamine possessed fewer side effects on the normal tissue compared with MTX. The prodrug micelle showed four advantages: retention of the drug activity site, higher water solubility of methotrexate (MTX), ease of preparation and application, and preferential accumulation in tumor tissues. These advantages of MTX-mPEG make it a promising drug delivery system (DDS) for clinical use.