C-peptide-functionalized SLNs co-delivering Paclitaxel and Quercetin significantly reduce TNBC tumor growth

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy characterized by the absence of estrogen, progesterone, and HER2 receptors, leading to a paucity of molecular targets and pronounced therapeutic recalcitrance. Current chemotherapy, often involving paclitaxel (PTX), is limited by poor tumor targeting, systemic toxicity, and drug resistance. Quercetin (Q) has shown promise as a complementary agent, but its clinical utility is hampered by poor solubility and rapid clearance. A targeted delivery system is critically needed to enhance the efficacy and reduce the side effects of these agents in TNBC.

Researchers developed C-peptide-functionalized solid lipid nanoparticles (SLNs) to co-deliver Paclitaxel and Quercetin (SLN-PTX-Q-pep) to αvβ3-expressing TNBC cells. The optimized formulation was characterized for morphology, size (mean hydrodynamic diameter of approximately 415 nm), and encapsulation efficiency. In vitro studies used 4T1 TNBC cells to assess IC50 values, apoptosis (Annexin V staining), cell migration, and reactive oxygen species (ROS) suppression. Competitive binding assays verified specific interaction with the αvβ3 integrin receptor. In vivo, SPECT imaging tracked tumor accumulation, and mice were treated with SLN-PTX-Q-pep to evaluate tumor growth, body weight, serum biochemistry, and organ histology for systemic toxicity.

The SLN-PTX-Q-pep formulation achieved high encapsulation efficiencies for both PTX (96.9 ± 0.6%) and Q (91.8 ± 1.5%). It demonstrated excellent blood compatibility with less than 1.5% hemolysis and exhibited pH-responsive drug release, accelerating under mildly acidic, tumor-relevant conditions (pH 5.8). In vitro, the targeted nanoformulation achieved a lower PTX IC50 value in 4T1 TNBC cells compared to nontargeted controls. Functional assays confirmed enhanced apoptosis, reduced cell migration, and suppression of intracellular ROS. Competitive binding assays verified specific interaction with the αvβ3 integrin receptor. In vivo, SPECT imaging showed superior tumor accumulation of the targeted nanoparticles. Importantly:

Mice treated with SLN-PTX-Q-pep showed a significant reduction in tumor growth and lower final tumor burdens, with no signs of systemic toxicity as confirmed by stable body weight, serum biochemistry, and histological analysis of major organs.