Dual-Action Theranostic Nanoparticles Delivering Toll-Like Receptor 2 Inhibitors and Chemotherapy Target Breast...

Area of Science:

• Oncology
• Nanotechnology
• Immunology

Background:

• Breast cancer is a leading cause of cancer death in women, often due to therapy resistance.
• Tumor microenvironment (TME) and tumor-intrinsic factors contribute to resistance.
• Toll-like receptor 2 (TLR2) overexpression promotes breast cancer progression and chemoresistance, making it a therapeutic target.

Purpose of the Study:

• To develop a targeted nanoparticle-based therapy combining a TLR2 inhibitor and doxorubicin for breast cancer.
• To evaluate the efficacy of this combination therapy in preclinical breast cancer models.
• To investigate the mechanisms underlying the synergistic anti-cancer effects.

Main Methods:

• Developed hybrid poly(lactic-co-glycolic acid)-lipid nanoparticles (PLGA-CU) loaded with TLR2 inhibitor CU-CPT22.
• Developed liposomes (LIPO-DOXO) encapsulating doxorubicin.
• Functionalized both nanoparticle types with cyclic RGD peptides for αvβ3 integrin targeting.
• Assessed efficacy in vitro on breast cancer cells and in vivo in 4T1 tumor-bearing mice.

Main Results:

• PLGA-CU effectively inhibited TLR2 signaling.
• Combined PLGA-CU and LIPO-DOXO reduced cell viability and induced apoptosis more than monotherapies.
• In vivo, nanoparticles accumulated in tumors, and combination therapy reduced tumor growth, angiogenesis, and immunosuppression.
• The combination therapy demonstrated enhanced anti-tumor activity.

Conclusions:

• Nanoparticle-mediated delivery of a TLR2 inhibitor and doxorubicin yields synergistic anti-cancer effects in breast cancer.
• This strategy holds promise for overcoming chemoresistance and improving treatment outcomes in advanced breast cancer.
• The dual-drug nanoparticle approach represents a potential new therapeutic strategy for breast cancer.