Vol. 1 No. 1 (2025)

Articles

Near-Infrared Quantum Dot-Conjugated Nanobodies for Dual-Modal Fluorescence Imaging and Photodynamic Therapy of HER2-Positive Breast Cancer

Published 2025-08-13

  • Sophia R. Pate

Sophia R. Pate
Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, 8093, Switzerland

Abstract

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for 15–20% of all breast cancer cases and is associated with aggressive progression and poor prognosis. Current diagnostic methods (e.g., immunohistochemistry, FISH) lack real-time imaging capabilities, while therapeutic strategies (e.g., trastuzumab) often suffer from low tumor penetration and acquired resistance. Herein, we report a dual-modal nanotherapeutic probe based on near-infrared (NIR) quantum dots (QDs) conjugated with anti-HER2 nanobodies (Nb) and photosensitizers (PS) for simultaneous fluorescence imaging and photodynamic therapy (PDT) of HER2-positive breast cancer. The NIR QDs (CdSe/ZnS core-shell, emission wavelength: 808 nm) were synthesized via a hot-injection method, surface-modified with polyethylene glycol (PEG) to enhance biocompatibility, and conjugated with anti-HER2 Nb (high-affinity, small-size targeting ligands) and chlorin e6 (Ce6, a photosensitizer) via click chemistry. The resulting Nb-QD-Ce6 probe exhibits excellent photostability, high HER2 targeting specificity, and efficient reactive oxygen species (ROS) generation under NIR laser irradiation (660 nm). In vitro studies show that Nb-QD-Ce6 achieves 4.2-fold higher cellular uptake in SK-BR-3 HER2-positive breast cancer cells than non-targeted QD-Ce6, enabling clear NIR fluorescence imaging (signal-to-noise ratio: 12.8) and efficient PDT-induced cell apoptosis (apoptotic rate: 78.5%). In vivo, Nb-QD-Ce6 provides real-time visualization of HER2-positive tumors in xenograft mice, with a tumor-to-muscle signal ratio of 8.7 at 24 h post-injection. PDT treatment with Nb-QD-Ce6 + 660 nm laser significantly inhibits tumor growth (tumor volume reduction: 76.3% vs. saline control) and prolongs mouse survival (median survival: 42 days vs. 21 days for saline). This work demonstrates the potential of NIR QD-nanobody conjugates as a versatile platform for integrated tumor imaging and targeted therapy, bridging nanomaterial optics, antibody engineering, and cancer therapeutics for precision oncology.

Keywords

Quantum Dots; Nanobodies; HER2-Positive Breast Cancer; Fluorescence Imaging; Photodynamic Therapy; Near-Infrared; Tumor Targeting; Reactive Oxygen Species

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