Near-Infrared Fluorescence Imaging and Photothermal Therapy of Tumors Using a Targeted Helical Protein Scaffold

Area of Science:

• Biotechnology
• Nanomedicine
• Cancer Therapy

Background:

• Photothermal therapy (PTT) using near-infrared (NIR) agents shows promise for tumor ablation.
• Current PTT platforms often use nanoparticles or polymers, limiting targeting precision and dye loading control.

Purpose of the Study:

• To design a modular protein scaffold for site-specific conjugation of NIR dyes.
• To develop a targeted platform for enhanced fluorescent imaging and PTT of HER2-positive tumors.

Main Methods:

• Engineered an eight-helix protein scaffold with 20 cysteine residues for covalent dye attachment.
• Conjugated the NIR dye AQuora800-maleimide to the scaffold.
• Incorporated HER2-targeting ligands, identifying an affibody dimer construct (AD-20AQ) as optimal.
• Evaluated in vivo pharmacokinetics and PTT efficacy in a 4T1 murine tumor model.

Main Results:

• AD-20AQ demonstrated enhanced tumor accumulation and retention in HER2-positive tumors compared to controls.
• Intravenous administration of AD-20AQ followed by 808 nm laser irradiation achieved complete tumor ablation in vivo.
• The targeted protein scaffold proved effective for both imaging and PTT.

Conclusions:

• Targeted, labeled protein scaffolds represent a versatile platform for advanced cancer imaging and therapy.
• This approach offers improved precision and control over dye loading for PTT applications.
• The AD-20AQ construct shows significant potential for clinical translation in HER2-targeted cancer treatment.