Doxorubicin-Loaded Micelle Targeting MUC1: A Potential Therapeutic for MUC1 Triple Negative Breast Cancer Treatment
Methods: From many candidate peptides, QNDRHPR-GGGSK (QND) and HSQLPQV-GGGSK (HSQ) were identified computationally, synthesized and purified using solid phase peptide synthesis and semipreparative HPLC. The peptides showed significant high binding to MUC1 expressing cells using a fluorescent microscope. The peptides were then conjugated on pegylated octadecyl lithocholate copolymer. DOX-encapsulated micelles were formed through self-assembly. MUC1-targeted micelles were characterized using dynamic light scattering (DLS) and Transmission Electron Microscopy (TEM). Drug entrapment efficiency was examined using a microplate reader. Cytotoxicity, binding, and uptake were also investigated.
Results: Two types of DOX-loaded micelles with different targeting peptides, QND or HSQ, were developed. DOX-loaded micelles were spherical in shape with average particle size around 300-320 nm. Drug entrapment efficiency of untargeted and targeted DOX micelles was about 71-93%. Targeted QND-DOX and HSQ-DOX micelles exhibited significantly higher cytotoxicity compared to free DOX and untargeted DOX micelles on BT549-Luc cells. In addition, significantly greater binding and uptake were observed for QND-DOX and HSQ-DOX micelles on BT549-Luc and T47D cells.
Conclusion: Taken together, these results suggested that QND-DOX and HSQ-DOX micelles have a potential application in the treatment of TNBC-expressing MUC1.
Document Type: Research Article
Publication date: March 1, 2018
This article was made available online on August 28, 2017 as a Fast Track article with title: "Doxorubicin-Loaded Micelle Targeting MUC1: A Potential Therapeutic for MUC1 Triple Negative Breast Cancer Treatment".
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