Potentiating Paclitaxel with its Homologous Nanovesicles: A Synergistic Strategy for Triple-Negative Breast Cancer...

Area of Science:

• Biotechnology
• Cancer Research
• Nanomedicine

Background:

• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its invasive nature and limited treatment options.
• Paclitaxel (PTX) is a key chemotherapy agent, but its efficacy can be limited in TNBC.
• Natural products and nanocarriers offer potential for novel therapeutic strategies.

Purpose of the Study:

• To develop and evaluate natural extracellular nanovesicles from Taxus leaves (TLENs) as targeted therapy carriers for TNBC.
• To investigate the synergistic effects of TLENs combined with paclitaxel (PTX) for TNBC treatment.
• To elucidate the underlying mechanisms of action for TLENs and their combination therapy.

Main Methods:

• Development of TLENs from Taxus leaves and characterization of their composition (e.g., flavonoids, naringenin via LC-MS/MS).
• In vitro assessment of TLENs' anti-TNBC effects, cellular uptake mechanisms (macropinocytosis), and impact on signaling pathways (ROS, JNK/p38 MAPK).
• In vivo evaluation of the combined TLENs and PTX therapy on tumor microenvironment modulation, immune cell infiltration, and overall anti-tumor efficacy.

Main Results:

• TLENs demonstrated significant intrinsic anti-TNBC activity and enhanced sensitivity to paclitaxel.
• TLENs induced apoptosis and inhibited proliferation, epithelial-mesenchymal transition, and migration in TNBC cells.
• Oral coadministration of TLENs and PTX reversed tumor immunosuppression, promoted anti-tumor immune responses (CD8+ T cells), and depleted suppressive cells (Tregs, MDSCs).

Conclusions:

• The "homologous combination" strategy using TLENs and PTX offers a novel and effective therapeutic approach for TNBC.
• TLENs act as potent nanocarriers that enhance paclitaxel efficacy and modulate the tumor immune microenvironment.
• This approach provides a promising platform for developing improved combination therapies for triple-negative breast cancer.