Glutathione-Exhausting Nanoprobes for NIR-II Fluorescence Imaging-Guided Surgery and Boosting Radiation Therapy Efficacy via Ferroptosis in Breast Cancer

Breast-conserving surgery (BCS) is the standard of carefor earlybreast cancer patients, while the high ratio of reoperation is stilla challenge due to inaccurate margin assessments. In patients withlocally advanced or advanced breast cancer, radiotherapy is an importanttreatment for local control or improvement of quality of life. However,enhancing sensitization to radiotherapy is an unmet medical need.To solve the above clinical predicaments, a glutathione (GSH) exhaustingvirus-like silicon dioxide nanoprobe with Gd coating and folic acid(FA) modification is designed. After loading ICG in the mesopores,the VGd@ICG-FA probe efficiently targets tumor cells with high resolution,due to its virus-like morphology and folate acid anchoring. Especially,the fabricated nanoprobe enables the identification of tiny cancersand navigates precise surgery under NIR-II fluorescence imaging. Moreover,after the nanoprobes enter into the cytoplasm of cancer cells, tetrasulfidelinkages in the silica framework are broken under the triggering ofhigh GSH concentrations. In turn, the broken framework exhausts GSHto disrupt intracellular reactive oxygen species (ROS) homeostasis,and Gd produces more ROS under radiotherapy, further activating ferroptosis,and resulting in the enhancement of radiotherapy in breast cancer.Therefore, our nanoprobe exhibits tremendous potential as a NIR-IIfluorescence imaging agent with no systematic side effects for precisecancer surgery and nanotherapeutics for boosting radiation sensitivityin future clinical translation of breast cancer.