A Carrier-Free Nanomedicine Enables Apoptosis-Ferroptosis Synergistic Breast Cancer Therapy by Targeting Subcellular...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Cancer cell heterogeneity complicates treatment, particularly in triple-negative breast cancer (TNBC).
• Combining multiple cell death pathways, like apoptosis and ferroptosis, shows promise for sensitizing TNBC treatment.

Purpose of the Study:

• To design and evaluate carrier-free theranostic ASP nanoparticles for synergistic apoptosis and ferroptosis induction in TNBC.
• To investigate the self-assembly mechanism and tumor-targeting capabilities of ASP nanoparticles.

Main Methods:

• ASP nanoparticles were self-assembled from aurantiamide acetate (Aa), scutebarbatine A (SA), and palmitin (P) using noncovalent bonding.
• Enhanced permeability and retention (EPR) effects and mitochondrial-lysosomal targeting were utilized for tumor site accumulation.
• The synergistic effects of Aa, SA, and P on apoptosis, ferroptosis, p53 upregulation, and cancer cell uptake were analyzed.

Main Results:

• ASP nanoparticles demonstrated an ordered nanostructure through self-assembly.
• The nanoparticles effectively targeted tumor sites via EPR effects and mitochondrial-lysosomal pathways.
• Combined Aa, SA, and P induced both mitochondrial apoptosis and ferroptosis, upregulated p53, and enhanced nanoparticle uptake by cancer cells.

Conclusions:

• The self-assembled ASP nanoparticles represent a novel nanomedicine design strategy using multiple natural products.
• The synergistic action of Aa, SA, and P within ASP nanoparticles leads to potent anticancer effects against TNBC.
• ASP nanoparticles hold significant potential for the theranostic treatment of triple-negative breast cancer.