Dual drug delivery of trapoxin A and methotrexate from biocompatible PLGA-PEG polymeric nanoparticles enhanced antitumor activity in breast cancer cell line

Abstract Nanoparticle (NP) mediated systems have been considered for chemotherapeutical delivery because of their ability to control drug release and reduce side effects These systems can also be used to deliver two or more drugs at the same time and prevent the growth of resistant cancer cells. Trapoxin A (TPX) and methotrexate (MTX) have shown promising results in treatment or controlling the progression of cancer. The present study examines the synergistic anticancer efficiency of TPX and MTX co-loaded PLGA-PEG NPs against MCF-7 breast cancer cells. The resultant drug-loaded PLGA-PEG NPs displayed a spherical morphology with the uniform nanosize distribution. Besides, the possible mechanisms for the inhibition of cell growth, distribution of cell cycle, and induction of apoptotic cell death were analyzed by DAPI staining, cell cycle analysis, and qRT-PCR. Interestingly, the obvious synergistic anticancer effects and the activation of the mitochondrial apoptosis pathway were observed on the breast cancer cell line MCF-7 by treating with TPX/MTX-co-loaded PLGA-PEG NPs. Also, it was revealed that the dual drug-loaded NPs could considerably change the expression levels of cyclin D1, and Bcl-2 compared to the free combination of the drugs as well as the single drug-loaded NPs. Taken together, this work revealed that TPX/MTX co-loaded PLGA-PEG NP based combination therapy might have an important potential to increase the efficiency of breast cancer therapy.