A Supramolecular, Triple Negative Breast Cancer-Targeting Avidin-Photosensitizer.

Area of Science:

• Bioconjugate chemistry
• Cancer therapy
• Nanomedicine

Background:

• Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating novel treatment approaches.
• Photodynamic therapy (PDT) shows potential but suffers from poor photosensitizer selectivity and cellular uptake.
• Targeted delivery of photosensitizers is crucial for enhancing PDT efficacy in TNBC.

Purpose of the Study:

• To develop a targeted delivery system for photosensitizers in TNBC.
• To enhance cellular uptake and phototoxicity of photosensitizers in TNBC cells.
• To create a novel bioconjugate for targeted photodynamic therapy.

Main Methods:

• Preparation of a Ru-NH2-modified avidin bioconjugate (RuAvi) via Tyr-specific modification.
• Assembly of RuAvi with a cinnamoyl peptide (FK) that targets the formyl peptide receptor 1 overexpressed in TNBC.
• Evaluation of the bioconjugate's binding affinity, cellular uptake, and phototoxicity in TNBC cells and tumor spheroids.

Main Results:

• The assembled FK4-RuAvi bioconjugate demonstrated enhanced binding and significantly lower IC50 values (0.36 µM) compared to RuAvi alone (1.25 µM) in MDA-MB-231 cells upon irradiation.
• FK4-RuAvi showed efficient uptake in MDA-MB-231 tumor spheroids.
• Irradiated FK4-RuAvi exhibited significant toxicity in TNBC models.

Conclusions:

• The developed FK4-RuAvi bioconjugate effectively targets TNBC cells by leveraging the formyl peptide receptor 1.
• This targeted delivery strategy enhances photosensitizer uptake and photodynamic therapy efficacy.
• The approach holds promise for developing targeted adjuvant treatments for TNBC.