Self‐Assembled Peptide‐Gold Nanoclusters with SiRNA Targeting Telomeric Response to Enhance Radiosensitivity in Lung Cancer Cells
Sean Moro, Mir Davood Omrani, Sule Erbek, Muriel Jourdan, Catharina I. Vandekerckhove, Cyril Nogier, Laetitia Vanwonterghem, Marie‐Carmen Molina, Pau Bernadó, Aurélien Thureau, Jean‐Luc Coll, Olivier Renaudet, Xavier Le Guével, Virginie Faure
Abstract
Lung cancer cells resistant to radiotherapy present a significant clinical challenge. Stable telomeric structures, maintained by the TRF2 protein, play a critical role in protecting cells from ionizing radiation. Reduced TRF2 expression increases DNA damage and radiosensitivity. We designed a self-assembling system utilizing ultra-small luminescent gold nanoclusters (AuNCs) with radiosensitizing properties, combined with siRNA targeting TRF2. The system forms ≈100 nm non-spherical structures with AuNCs enriched in the outer layer, exhibiting a 17.6-fold enhancement in red photoluminescence due to aggregation-induced effects. This nanoplatform efficiently penetrates lung cancer cells, reducing TRF2 expression by 50%. Under 5 Gy radiotherapy, cells treated with this system show a 1.5-fold radiosensitivity increase from AuNCs and a 2.3-fold reduction in clonogenic survival due to telomere deprotection. The AuNC-siRNATRF2 system combines enhanced optical properties with biological functionality, offering a promising approach to augment radiotherapy efficacy by disrupting telomeric protective mechanisms in cancer cells.