GSH-responsive nanomedicine for disease smart imaging and therapy

Glutathione (GSH) is a main component of the antioxidant system in organisms, scavenging reactive oxygen species and protecting cells from oxidative stress, thus playing important roles in many physiological processes. An imbalance of GSH level within the microenvironment is a characteristic of many diseases, which makes this biochemical property of the disease site be exploited as a potential target for disease treatment. Recent advances in nanomedicine have led to a proliferation of nanomedicines targeting GSH, with which a variety of emerging imaging and therapeutic modalities have been achieved on multiple disease models. Here, we review recent advances in nanomedicine for diseases characterized by imbalanced GSH levels. First, the design strategies and chemical mechanisms of GSH-responsive nanomedicine are described. Then, we provide a systematic review of the application of GSH-responsive nanomaterials for disease smart imaging including fluorescence imaging, photoacoustic imaging, magnetic resonance imaging and computed tomography imaging. Moreover, GSHresponsive nanomaterials-based tumor smart therapeutic strategies including chemotherapy, phototherapy, chemo-dynamic therapy and ferroptosis are detailedly introduced. An in-depth discussion of current challenges and future prospects for GSH-responsive nanomedicine are given at the end of this review.