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

Abstract

Breast-conserving surgery (BCS) is the standard of care for early breast cancer patients, while the high ratio of reoperation is still a challenge due to inaccurate margin assessments. In patients with locally advanced or advanced breast cancer, radiotherapy is an important treatment 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) exhausting virus-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 cancers and navigates precise surgery under NIR-II fluorescence imaging. Moreover, after the nanoprobes enter into the cytoplasm of cancer cells, tetrasulfide linkages in the silica framework are broken under the triggering of high GSH concentrations. In turn, the broken framework exhausts GSH to 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-II fluorescence imaging agent with no systematic side effects for precise cancer surgery and nanotherapeutics for boosting radiation sensitivity in future clinical translation of breast cancer.

Tumor microenvironment-responsive degradable silica nanoparticles: design principles and precision theranostic applications

“…Similarly, Wei et al 112 designed a virus-like mesoporous silica nanoprobe (VGd@ICG-FA) capable of achieving NIR-II fluorescence imaging and inducing ferroptosis by RT sensitization. The nanoprobe was obtained by utilizing tetrasulfide-bridged silica nanoparticles to load the photosensitizer ICG, which was then coated with gadolinium (Gd) and anchored with FA.…”

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

“…Moreover, GSH concentration in tumor tissues is reported to be over four times higher than in normal tissues, [ 114,115 ] making it possible for designing GSH‐responsive nanomaterials to reduce GSH levels in tumor tissues and enhance radio‐sensitization effects. [ 116–118 ] This chapter systematically discusses two distinct responsive mechanisms of GSH‐triggered radiosensitizers, namely disassembly and aggregation, for enhanced radiotherapy efficiency. GSH‐triggered disassembly is referred to the disassociation of nanocomposite into small‐sized nanoparticles to penertrate the deeper tumor tissues for sensitizing RT in the overexpressed GSH of TME.…”

Boosting antitumor immunity via a tumor microenvironment-responsive transformable trifecta nanovaccine

“…Remarkably, the transformation ratio significantly increased upon the administration of GSH, and the degradation and transformation behavior displayed a positive correlation with the concentration of GSH. GSH, even at a concentration of 2.5 mM, exhibited the capability to transform ~90% of TriNC into sTriNC, suggesting that TriNC could efficiently exhaust GSH to reshape the TME 16 . TriNV was then obtained by loading ICG into the TriNC.…”