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Updated: Jan 1, 2026
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Engineering a Nanostructured Nucleolin-Binding Peptide for Intracellular Drug Delivery in Triple-Negative Breast
Mireia Pesarrodona1, Laura Sánchez-García1, Joaquin Seras-Franzoso
1CIBER de Bioingeniería , Biomateriales y Nanomedicina (CIBER-BBN) , C/ Monforte de Lemos 3-5 , 28029 Madrid , Spain.
Abstract:
Five peptide ligands of four different cell surface receptors (nucleolin, CXCR1, CMKLR1, and CD44v6) have been evaluated as targeting moieties for triple-negative human breast cancers. Among them, the peptide F3, derived from phage display, promotes the fast and efficient internalization of a genetically fused green fluorescent protein (GFP) inside MDA-MB-231 cancer stem cells in a specific receptor-dependent fashion. The further engineering of this protein into the modular construct F3-RK-GFP-H6 and the subsequent construct F3-RK-PE24-H6 resulted in self-assembling polypeptides that organize as discrete and regular nanoparticles. These materials, 15-20 nm in size, show enhanced nucleolin-dependent cell penetrability. We show that the F3-RK-PE24-H6, based on the Pseudomonas aeruginosa exotoxin A (PE24) as a core functional domain, is highly cytotoxic over target cells. The combination of F3, the cationic peptide (RK), and the toxin domain PE24 in such unusual presentation appears as a promising approach to cell-targeted drug carriers in breast cancers and addresses selective drug delivery in otherwise difficult-to-treat triple-negative breast cancers.
Insights
Researchers developed novel nanoparticles using the F3 peptide to target triple-negative breast cancer cells. These nanoparticles efficiently deliver cytotoxic payloads, offering a promising strategy for targeted cancer drug delivery.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges.
- Targeted drug delivery systems are crucial for improving treatment efficacy and reducing side effects.
- Peptide ligands offer potential for specific cancer cell targeting.
Purpose of the Study:
- To evaluate peptide ligands as targeting moieties for TNBC.
- To engineer self-assembling nanoparticles for enhanced drug delivery.
- To assess the cytotoxicity of engineered nanoparticles against cancer cells.
Main Methods:
- Phage display was used to identify peptide ligands.
- Genetic engineering created modular constructs (F3-RK-GFP-H6, F3-RK-PE24-H6).
- Nanoparticle characterization (size, self-assembly) and cell penetration studies were performed.
Main Results:
- The F3 peptide facilitated efficient internalization of cargo into cancer stem cells.
- Engineered constructs self-assembled into nanoparticles (15-20 nm).
- F3-RK-PE24-H6 nanoparticles demonstrated high cytotoxicity against target cells via nucleolin-dependent delivery.
Conclusions:
- Engineered nanoparticles show enhanced cell penetrability and targeted cytotoxicity.
- The F3-RK-PE24-H6 construct is a promising candidate for targeted drug carriers in TNBC.
- This approach addresses selective drug delivery for difficult-to-treat breast cancers.
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