Integrin αvβ3-Targeted SLNs for Co-Delivery of Paclitaxel and Quercetin in Triple-Negative Breast Cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to limited molecular targets and aggressive nature.
• Concurrent use of paclitaxel (PTX) and quercetin (Q) is hindered by poor solubility, rapid clearance, and toxicity.

Purpose of the Study:

• To develop a C-peptide-functionalized solid lipid nanoparticle (SLN) system for enhanced codelivery of PTX and Q to αvβ3-expressing TNBC cells.
• To evaluate the targeted nanoformulation's efficacy and safety in preclinical TNBC models.

Main Methods:

• Formulation of C-peptide-functionalized SLNs encapsulating PTX and Q (SLN-PTX-Q-pep).
• Characterization of nanoparticle morphology, size, drug encapsulation, and stability.
• In vitro assessment of drug release, cytotoxicity, apoptosis, migration, and ROS levels in 4T1 TNBC cells.
• In vivo evaluation using SPECT imaging for tumor accumulation and assessment of tumor growth, body weight, and organ histology.

Main Results:

• Optimized SLN-PTX-Q-pep showed high encapsulation efficiency and suitable particle size.
• The formulation demonstrated pH-responsive drug release and excellent blood compatibility.
• Targeted SLNs significantly reduced PTX IC50, enhanced apoptosis, reduced migration, and suppressed ROS in vitro.
• In vivo studies confirmed superior tumor accumulation, significant tumor growth inhibition, and no systemic toxicity.

Conclusions:

• C-peptide-functionalized SLNs provide a robust platform for coordinated PTX and Q delivery, enhancing tumor targeting and therapeutic efficacy in TNBC.
• This dual-drug nanocarrier system holds promise for treating difficult-to-treat breast cancers.