Background: Triple negative breast cancer (TNBC) is an aggressive disease associated with
poor prognosis and lack of validated targeted therapy. Thus chemotherapy is a main adjuvant treatment
for TNBC patients, but it associates with severe toxicities. For a better treatment outcome, we developed
an alternative therapeutic, doxorubicin (DOX)-loaded micelles targeting human mucin1 protein
(MUC1) that is less toxic, more effective and targeted to TNBC.
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.