Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Dual targeting strategies enhance cancer diagnosis and therapy by engaging both extracellular and intracellular tumor-specific receptors.
• Gold nanoclusters (AuNCs) offer a versatile platform for developing targeted nanomedicines due to their unique optical and chemical properties.

Purpose of the Study:

• To develop a novel dual-targeting nano-platform (AuNC-cRGD-Apt) for cancer imaging and therapy.
• To create a near-infrared (NIR) fluorescent probe (AuNC-MPA-cRGD-Apt) for tumor imaging.
• To design a dual-targeting prodrug (AuNC-DOX-cRGD-Apt) for enhanced cancer therapy.

Main Methods:

• Conjugation of gold nanocluster (AuNC) with cyclic RGD (cRGD) targeting αvβ3 integrins and AS1411 aptamer (Apt) targeting nucleolin.
• Functionalization of the nano-platform with a near-infrared (NIR) fluorescence dye (MPA) for imaging.
• Immobilization of Doxorubicin (DOX) onto the nano-platform to create a prodrug for chemotherapy.

Main Results:

• The NIR fluorescent probe AuNC-MPA-cRGD-Apt exhibited low cytotoxicity and effective tumor-targeting capabilities in vitro and in vivo.
• The dual-targeting prodrug AuNC-DOX-cRGD-Apt demonstrated enhanced tumor affinity, deep tumor penetration, and improved anti-tumor activity.
• Successful application in various tumor cell lines, tumor spheroids, and tumor-bearing mouse models.

Conclusions:

• Non-toxic AuNCs modified with dual targeting ligands hold significant potential for tumor-targeted imaging.
• Dual-targeting AuNCs serve as a promising core for designing effective prodrugs in cancer therapy.
• The developed nano-platform offers a viable strategy for advancing cancer diagnosis and treatment.