Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

Abstract

Radiotherapy (RT) has been a classical therapeutic method of cancer for several decades. It attracts tremendous attention for the precise and efficient treatment of local tumors with stimuli‐responsive nanomaterials, which enhance RT. However, there are few systematic reviews summarizing the newly emerging stimuli‐responsive mechanisms and strategies used for tumor radio‐sensitization. Hence, this review provides a comprehensive overview of recently reported studies on stimuli‐responsive nanomaterials for radio‐sensitization. It includes four different approaches for sensitized RT, namely endogenous response, exogenous response, dual stimuli‐response, and multi stimuli‐response. Endogenous response involves various stimuli such as pH, hypoxia, GSH, and reactive oxygen species (ROS), and enzymes. On the other hand, exogenous response encompasses X‐ray, light, and ultrasound. Dual stimuli‐response combines pH/enzyme, pH/ultrasound, and ROS/light. Lastly, multi stimuli‐response involves the combination of pH/ROS/GSH and X‐ray/ROS/GSH. By elaborating on these responsive mechanisms and applying them to clinical RT diagnosis and treatment, these methods can enhance radiosensitive efficiency and minimize damage to surrounding normal tissues. Finally, this review discusses the additional challenges and perspectives related to stimuli‐responsive nanomaterials for tumor radio‐sensitization.

Activatable Probes for Ratiometric Imaging of Endogenous Biomarkers In Vivo

“…The current clinical imaging for the noninvasive and quantitative detection of tumor biomarkers in vivo is still limited; however, GSH is a key biomarker of malignant tumors, and imaging some biomarkers such as GSH for understanding the progression of disease is crucial. − Recently, Gao and co-workers designed a GSH-responsive Fe 3 O 4 -based MRI ratiometric probe (NPS-S-PEP) for quantitative imaging of GSH in vivo (Figure a) . In the presence of GSH, the probe can form large Fe 3 O 4 aggregates within tumors due to the click reaction between the thiol group produced upon the reduction of the disulfide bond modified in the biocompatible ligand by GSH and the maleimide residue on the Fe 3 O 4 surface, giving rise to an enhanced T 2 contrast and a weakened T 1 contrast as well as GSH concentration-dependent interlocked relaxivities ( ΔR 2 /ΔR 1 ) due to the magnetic–magnetic interaction effect between the tightly adjacent Fe 3 O 4 NPs.…”