Key result
Doxorubicin/FA-PLGA-TFA NPs surpass standard AC regimen in antitumor efficacy while preserving heart health.
Why the study?
Standard doxorubicin/cyclophosphamide treatment for breast cancer is hindered by cancer cell resistance and regimen-induced side effects that reduce patient quality of life.
Does Dox/FA-PLGA-TFA NPs combination improve antitumor efficacy and safety compared to standard AC regimen in a DMBA-induced breast cancer model?
Does Dox/FA-PLGA-TFA NPs combination improve antitumor efficacy and safety compared to standard AC regimen in a DMBA-induced breast cancer model?
The Dox/FA-PLGA-TFA NPs combination demonstrated superior antitumor activity and a better safety profile, including cardioprotection, compared to the standard AC regimen in a preclinical breast cancer model.
Hypothesis-generating for nanoparticle doxorubicin in breast cancer; should not change practice pending human trials.
AIM: Doxorubicin/Cyclophosphamide (AC) is one of the standard adjuvant anthracycline-containing regimens that is still in use for breast cancer treatment. Cancer cell resistance and AC-induced side effects make treatment suboptimal and worsen patients' quality of life. This study aimed to improve trans-ferulic acid's (TFA) efficiency via loading into folate-receptor-targeted-poly lactic-co-glycolic acid nanoparticles (FA-PLGA-TFA NPs). Also, investigating both the antitumor efficacy of Doxorubicin (Dox)/FA-PLGA-TFA NPs combination against dimethylbenz[a]anthracene (DMBA)-induced breast cancer and its safety profile. METHODS: FA-PLGA-TFA NPs were optimally fabricated and characterized. Levels of Notch1, Hes1, Wnt-3a, β-catenin, MMP-9, cyclin D1, Permeability-Glycoprotein (P-gp), ERα, PR, and HER2 were assessed as a measure of the antitumor efficacy of different treatment protocols. Histopathological examination of heart and bone, levels of ALT, AST, ALP, CK-MB, and WBCs count were evaluated to ensure the combination's safety profile. KEY FINDINGS: Dox/FA-PLGA-TFA NPs not only inhibited Notch signaling but also suppressed Notch synergy with Wnt, estrogen, progesterone, and HER2 pathways. Interestingly, Dox/FA-PLGA-TFA NPs decreased P-gp level and preserved heart, bone, and liver health as well as WBCs count. SIGNIFICANCE: Dox/FA-PLGA-TFA NPs reduced the side-effects of each single drug, and at the same time exerted excellent antitumor activity that surpass the AC regimen in evading cancer cell resistance and having a superior safety profile.
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Helmy et al. (2021) studied DMBA-induced breast cancer. Doxorubicin/FA-PLGA-TFA NPs combination vs. Doxorubicin/Cyclophosphamide (AC) regimen was evaluated on Antitumor efficacy and safety profile. Doxorubicin/FA-PLGA-TFA NPs combination exerted excellent antitumor activity surpassing the standard AC regimen while demonstrating a superior safety profile by preserving heart, bone, and liver health.
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