PEG-modification enhances the targeted photothermal therapy of affibody-conjugated indocyanine green for precision cancer treatment.

Photothermal therapy (PTT) is an innovative cancer treatment that leverages heat generated from near-infrared light exposure to induce tumor cell death. A major challenge in PTT is achieving precise delivery of the photothermal agent to tumor tissues to maximize efficacy and minimize off-target effects. In this study, we introduce a novel ligand-coupled photothermal reagent that addresses this challenge by leveraging the high-affinity HER2 affibody Z _HER2:2891 (referred to as Z _HER2 ), conjugated with indocyanine green (ICG) for targeted delivery. Polyethylene glycol (PEG) was incorporated as a hydrophilic linker to further optimize photothermal conversion efficiency and enhance tumor-specific targeting. Among the conjugates tested, Z _HER2 -PEG ₁₀₀₀ -ICG, modified with a PEG chain of 1000 Da molecular weight, demonstrated exceptional performance. In vitro studies revealed that Z _HER2 -PEG ₁₀₀₀ -ICG specifically bound to HER2-expressing cells and effectively induced cell death. In vivo experiments using HER2-positive N87 tumor-bearing mice showed that Z _HER2 -PEG ₁₀₀₀ -ICG accumulated highly and specifically in tumor tissues over an extended period. Upon light irradiation, this conjugate caused a significant rise in temperature at the tumor site, resulting in complete tumor elimination with a single photothermal treatment. This PEG-modified affibody-ICG conjugate represents a precise and effective approach to PTT, offering a promising new therapeutic strategy for cancer treatment with the potential to significantly impact future cancer therapies.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)