Background: Treatment of metastatic cancer remains a formidable clinical challenge. Better therapeutic options with
improved tissue penetration and tumor cell uptake are urgently needed. Targeted nanotherapy, for improved delivery,
and combinatory drug administration aimed at inhibiting chemo-resistance may be the solution.
Purpose: The study was performed to evaluate the therapeutic efficacy of polymeric PEG-PE micelles, co-loaded with
curcumin (CUR) and doxorubicin (DOX), and targeted with anti-GLUT1 antibody (GLUT1) against MDA-MB-231
human breast adenocarcinoma cells both in vitro and in vivo.
Methods: MDA-MB-231 DOX-resistant cells were treated with non-targeted and GLUT1-targeted CUR and DOX
micelles as a single agent or in combination. Tumor cells were also inoculated in female nude mice. Established tumors
were treated with the micellar formulations at a dose of 6 mg/kg CUR and 1 mg/kg DOX every 2 d for a total of 7
Results: CUR+DOX-loaded micelles decorated with GLUT1 had a robust killing effect even at low doses of DOX in
vitro. At the doses chosen, non-targeted CUR and CUR+DOX micelles did not exhibit significant tumor inhibition
versus control. However, GLUT1-CUR and GLUT1-CUR+DOX micelles showed a significant tumor inhibition effect
with an improvement in survival.
Conclusion: We showed a dramatic improvement in efficacy between the non-targeted and GLUT1-targeted
formulations both in vitro and in vivo. Also, importantly, the addition of CUR to the micelle, has restored sensitivity to
DOX, with resultant tumor growth inhibition. Hence, we confirmed that GLUT1-CUR+DOX micelles are effective in
vitro and in vivo and deserve further investigation.