Inhibition of Multiple Myeloma Using 5-Aza-2ʹ-Deoxycytidine and Bortezomib-Loaded Self-Assembling Nanoparticles

PURPOSE: The aim of this study was to explore the use of self-assembling nanoparticles loaded with two chemotherapy drugs for the treatment of multiple myeloma. MATERIALS AND METHODS: Nanoparticle systems were developed based on amine polyethylene glycol-polycaprolactone (NH2-PEG-PCL) to encapsulate 5-Aza-2ʹ-deoxycytidine and Bortezomib using the self-assemble method. Morphological changes were observed by transmission electron microscopy (TEM), and the size, drug release, long-term stability, and release of reactive oxygen species (ROS) were analyzed. The MTT assay was used to evaluate the effects of drug-loaded nanoparticles (PEG-PCL-DAC-BTZ) in inhibiting the proliferation of multiple myeloma cells (U266 and LP-1), and the TUNEL assay and Western blotting were used to measure the induction of cell apoptosis. RESULTS: Based on the diameter of NH(2)-PEG-PCL and PEG-PCL-DAC-BTZ, the drug-loaded nanoparticles were successfully prepared. TEM revealed that PEG-PCL-DAC-BTZ was spherically shaped. More than 90% of the drugs were released after 72 h, and PEG-PCL-DAC-BTZ maintained a good stability. U266 and LP-1 cells treated with PEG-PCL-DAC-BTZ showed the highest growth inhibition, release of ROS, and cell apoptosis compared to those treated with unloaded nanoparticles and chemotherapy drugs alone. CONCLUSION: The drug-loaded nanoparticles are a good foundation for the treatment of multiple myeloma as they showed a slow release profile, good stability, and superior anti-cancer effects in vitro.