Dual-targeted fucoidan-TPP nanoparticles delivery system potently inhibit breast cancer via mitochondrial dysfunction...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Breast cancer presents significant therapeutic challenges including drug resistance and toxicity.
• Mitochondria are critical regulators of tumor apoptosis and immune responses.
• Novel strategies are needed to enhance targeted drug delivery and efficacy.

Purpose of the Study:

• To develop a dual-targeted nanodelivery system (FU@TPP/PTE Mn²⁺ NPs) for breast cancer treatment.
• To investigate the system's ability to target cancer cells via P-selectin and localize in mitochondria.
• To evaluate the co-delivery of pterostilbene (PTE) and manganese ions (Mn²⁺) for enhanced apoptosis and immune activation.

Main Methods:

• Development of fucoidan (FU) and triphenylphosphine (TPP) modified nanoparticles.
• In vitro studies using 4T-1 breast cancer cells to assess cellular uptake, mitochondrial localization, apoptosis induction, and cGAS-STING pathway activation.
• In vivo studies using a 4T1 breast cancer mouse model to evaluate tumor growth inhibition, metastasis reduction, and immune response modulation (dendritic cell maturation, CD8⁺ T cell infiltration).

Main Results:

• The FU@TPP/PTE Mn²⁺ NPs demonstrated successful dual targeting of cancer cells and mitochondria.
• In vitro experiments showed induction of mitochondrial-mediated apoptosis and activation of the cGAS-STING pathway.
• In vivo studies revealed significant inhibition of tumor growth, reduced lung metastasis, and enhanced anti-tumor immunity.

Conclusions:

• The developed dual-targeted nanodelivery system shows promise for overcoming breast cancer treatment limitations.
• Modulation of mitochondrial and immune pathways offers a viable strategy for advanced breast cancer therapy.
• FU@TPP/PTE Mn²⁺ NPs represent a potential therapeutic platform for enhancing breast cancer treatment outcomes.