Document Type

Article

Publication Date

3-2020

DOI

10.1016/j.apmt.2019.100492

Publication Title

Applied Materials Today

Volume

18

Pages

100492 (12 pp.)

Abstract

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

.© 2019 Elsevier Ltd. All rights reserved.

Comments

Research funded by:

National Science Foundation (NSF) Grant Number CBET-1701363

United States Department of Health & Human Services National Institutes of Health (NIH) - USA Grant Number R35GM133795

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

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