Intelligent responsive nanogels: New Horizons in cancer therapy

Biologically engineered nanogels formed through sophisticated intramolecular crosslinking processes represent the forefront of next-generation drug delivery systems. These innovative systems offer many advantages, like adjustable size, satisfactory biocompatibility, and minimal toxicity. Their unique attributes facilitate deep penetration and long-term retention of drugs in tumors, effectively enhancing the anti-tumor effects. Nonetheless, the rapid disintegration of nanogels and the subsequent triggering of drug release at the tumor site pose significant challenges in achieving more effective and precise tumor treatments. Therefore, increasing research has been dedicated to exploring stimulus-responsive nanogels for enhancing tumor therapy. This review aims to encapsulate the research advancements in emerging stimulus-responsive antitumor nanogels. Firstly, a detailed exposition is provided on various endogenous stimulus-responsive nanogels, encompassing factors such as pH, hypoxia, enzymes, reactive oxygen species (ROS), and glutathione (GSH). Secondly, various nanogels triggered by exogenous stimuli such as light, ultrasound, temperature, and magnetic fields are elaborately presented. Furthermore, nanogels with multifaceted stimulus-responsive properties are also skillfully designed. Finally, the future directions, application prospects, and challenges of intelligent responsive nanogels in cancer treatment are highlighted.