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

Cancer Manag Res. 2020 Aug 6:12:6969-6976. doi: 10.2147/CMAR.S255682. eCollection 2020.

Abstract

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-2'-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 NH2-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.

Keywords: 5-Aza-2ʹ-deoxycytidine; Bortezomib; multiple myeloma; nanoparticle.

Grants and funding

This work was supported by grants from Medical Research Youth Innovation Project of Sichuan Province (Q18017).