Applied Materials Today
100492 (12 pp.)
Disulfiram (DSF) is currently tested in several clinical trials for cancer treatment in combination with cop-per (Cu) ions. Usually, DSF and Cu are administered in two separate formulations. In the body, DSF andCu ions form diethyldithiocarbamate copper complex [Cu(DDC)2] which has potent antitumor activities.However, the “two formulation” approach often achieved low Cu(DDC)2 concentration at tumor regions and resulted in compromised anticancer efficacy. Therefore, preformed Cu(DDC)2 complex administered in a single formulation will have better anticancer efficacy. However, the poor aqueous solubility of Cu(DDC)2 is a significant challenge for its clinical use. In this work, a biomimetic nanoparticle formulation of Cu(DDC)2 was produced with a novel SMILE (Stabilized Metal Ion Ligand complex) method developed in our laboratory to address the drug delivery challenges. The Metal-organic Nanoparticle (MON) is composed of Cu(DDC)2 metal-organic complex core and surface decorated bovine serum albumin (BSA). Importantly, we designed a 3D-printed microfluidic device to further improve the fabrication of BSA/Cu(DDC)2 MONs. This method could precisely control the MON preparation process and also has great potential for large scale production of Cu(DDC)2 MON formulations. We also used a computational modeling approach to simulate the MON formation process in the microfluidic device. The optimized BSA/Cu(DDC)2 MONs demonstrated good physicochemical properties. The MONs also showed potent antitumor activities in the breast cancer cell monolayers as well as the 3D-cultured tumor spheroids. The BSA/Cu(DDC)2 MONs also effectively inhibited the growth of tumors in an orthotopic 4T1 breast tumor model. This current study provided a novel method to prepare a biomimetic MON formulation for DSF/Cu cancer therapy
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Original Publication Citation
Chang, Y., Jiang, J., Chen, W., Yang, W., Chen, L., Chen, P., ... & Hong, L. (2020). Biomimetic metal-organic nanoparticles prepared with a 3D-printed microfluidic device as a novel formulation for disulfiram-based therapy against breast cancer. Applied Materials Today, 18, 100492. doi: 10.1016/j.apmt.2019.100492
Chang, Ya; Jiang, Jizong; Chen, Wu; Yang, Wen; Chen, Lili; Chen, Pengyu; Shen, Jianzhong; Qian, Shizhi; Zhou, Teng; Wu, Linfeng; Hong, Liang; Huang, Yongzhuo; and Li, Feng, "Biomimetic Metal-Organic Nanoparticles Prepared with a 3D-Printed Microfluidic Device as a Novel Formulation for Disulfiram-Based Therapy Against Breast Cancer" (2020). Mechanical & Aerospace Engineering Faculty Publications. 96.