Targeted Therapy for CD13-Overexpressing Triple-Negative Breast Cancers Using Apoptosis-Inducing Protein Cage...

Area of Science:

• Oncology
• Nanotechnology
• Molecular Biology

Background:

• Triple-negative breast cancer (TNBC) lacks specific molecular targets, complicating treatment.
• Cluster of differentiation 13 (CD13) is a cell surface aminopeptidase overexpressed in tumors, promoting cancer progression.
• CD13's role in angiogenesis, proliferation, invasion, and metastasis makes it a potential therapeutic target.

Purpose of the Study:

• To investigate CD13 as a therapeutic target in TNBC.
• To develop and evaluate a dual-ligand protein cage nanoparticle for targeted TNBC therapy.

Main Methods:

• Engineered a protein cage nanoparticle (AaLS/TRAIL/aCD13Nb) displaying CD13-binding nanobodies (aCD13Nb) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
• Utilized the SpyCatcher/SpyTag system for protein ligation.
• Tested nanoparticle binding and efficacy in TNBC cell lines (HCC1937, MDA-MB-468, BT-549) and an HCC1937 xenograft mouse model.

Main Results:

• The dual-ligand nanoparticle demonstrated enhanced and specific binding to CD13-overexpressing TNBC cells.
• Nanoparticle-mediated binding facilitated TRAIL interaction with death receptors, activating apoptotic signaling.
• Significant therapeutic efficacy was observed in vitro and in vivo, with marked tumor growth suppression in mice and no systemic toxicity.

Conclusions:

• CD13 is validated as a promising therapeutic target for triple-negative breast cancer.
• Dual-ligand protein cage nanoparticles represent an effective platform for targeted cancer therapy.
• This strategy offers a novel approach for treating challenging TNBC subtypes.