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Advancing triple-negative breast cancer treatment through peptide decorated solid lipid nanoparticles for paclitaxel
Tahereh Rahdari1, Mohsen Mahdavimehr2, Hossein Ghafouri3
1Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
Abstract:
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 IC50 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.
Insights
This study introduces C-peptide-conjugated solid lipid nanoparticles (C-peptide-SLNs) for targeted paclitaxel delivery in triple-negative breast cancer (TNBC). This novel approach significantly reduced tumor growth and metastasis while minimizing toxicity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) is aggressive with limited therapeutic options.
- Targeted drug delivery systems are crucial for enhancing treatment efficacy and reducing side effects.
- Integrin αvβ3 receptors are overexpressed on TNBC cells, presenting a potential therapeutic target.
Purpose of the Study:
- To develop and evaluate C-peptide-conjugated solid lipid nanoparticles (C-peptide-SLNs) for targeted delivery of paclitaxel (PTX) in TNBC.
- To assess the efficacy and safety of C-peptide-SLN-PTX in preclinical models of TNBC.
Main Methods:
- C-peptide-SLNs were synthesized and characterized for particle size, stability, and drug encapsulation efficiency (>90%).
- In vitro cytotoxicity and cell migration assays were performed using TNBC cell lines (4T1, MDA-MB-231).
- In vivo efficacy was evaluated in 4T1 tumor-bearing mice, including tumor volume measurement, metastasis assessment, PET imaging, and immunohistochemical analysis.
Main Results:
- C-peptide-SLN-PTX demonstrated significantly enhanced in vitro cytotoxicity (IC50 = 1.2 µg/mL) compared to SLN-PTX and free PTX.
- The nanoparticles effectively inhibited TNBC cell migration and confirmed targeting of αv integrin receptors.
- In vivo studies showed an 82% reduction in tumor volume, prevention of pulmonary metastasis, and reduced systemic toxicity.
- PET imaging and immunohistochemistry confirmed superior antitumor efficacy, reduced proliferation (Ki-67), and induced apoptosis (p53, Bcl-2).
Conclusions:
- C-peptide-SLNs represent a promising targeted drug delivery system for paclitaxel in TNBC treatment.
- This strategy enhances therapeutic efficacy by leveraging C-peptide's affinity for integrin αvβ3 receptors.
- The findings suggest a potential for improved TNBC treatment with reduced side effects.
