Atomically-precise Au₂₂(Lys-Cys-Lys)₁₆ nanoclusters for radiation sensitization

Area of Science:

• Nanomedicine
• Biochemistry
• Radiotherapy

Background:

• Radiotherapy is crucial for cancer treatment but causes collateral damage to healthy tissues.
• Radiosensitizers enhance radiotherapy efficacy while minimizing harm to normal cells.

Purpose of the Study:

• To evaluate the radiosensitization potential, pharmacokinetics, biodistribution, and toxicity of Au22(Lys-Cys-Lys)16 nanoclusters.
• To investigate the mechanisms underlying the radiosensitizing effects of these gold nanoclusters.

Main Methods:

• Synthesis of atomically precise gold nanoclusters (Au22(Lys-Cys-Lys)16) via photochemical methods.
• In vitro and in vivo evaluation of radiosensitization in various cancer cell lines and animal models.
• Pharmacokinetic, biodistribution, and toxicity assessments.

Main Results:

• Au22(Lys-Cys-Lys)16 nanoclusters demonstrated high stability, efficient tumor cell internalization, and significant dose enhancement factors (2.0 in KB, 1.6 in 4T1 cells).
• Mechanistic studies revealed enhanced radiation-induced DNA damage and disrupted DNA repair pathways.
• In vivo studies showed delayed tumor progression and prolonged survival in a KB tumor-bearing mouse model with no observed side effects.

Conclusions:

• Au22(Lys-Cys-Lys)16 nanoclusters show significant radiosensitizing potential, offering a promising strategy for enhancing cancer radiotherapy.
• These nanoclusters exhibit favorable pharmacokinetic properties and renal clearance, suggesting clinical translatability.