Advancing triple-negative breast cancer treatment through peptide decorated solid lipid nanoparticles for paclitaxel delivery.

Triple-negative breast cancer (TNBC) presents a global health challenge due to its aggressive behavior and limited treatment options. This study explores a novel therapeutic strategy using C-peptide-conjugated solid lipid nanoparticles (C-peptide-SLNs) for targeting paclitaxel (PTX) delivery in TNBC treatment. C-peptide, derived from endostatin, enhances efficacy by targeting overexpressed integrin αvβ3 receptors on TNBC cells. Characterization confirmed suitable particle size, stability, and encapsulation efficiency over 90%, with favorable release profiles for acidic tumor environments. In vitro, C-peptide-SLN-PTX markedly improved cytotoxicity against 4T1 carcinoma cells, with an IC of 1.2 µg/mL, compared to 3.4 µg/mL for SLN-PTX and 8.9 µg/mL for free PTX. Wound-healing assays verified significant inhibition of cell migration in 4T1 and MDA-MB-231 cell lines. Flow cytometry confirmed αv integrin targeting by C-peptide-SLN-PTX. In vivo studies in 4T1 tumor-bearing mice showed an 82% tumor volume reduction and prevented pulmonary metastasis, with normal liver enzyme levels indicating reduced toxicity. PET imaging revealed decreased tumor metabolic activity in treated groups, and immunohistochemical analyses demonstrated superior antitumor efficacy with reduced Ki-67 expression and apoptosis induction (p53 upregulation, Bcl-2 downregulation). These findings highlight the potential of C-peptide-SLNs as an effective targeted PTX delivery system for TNBC, offering promising avenues for enhancing cancer treatment strategies.