Recent advances in redox-responsive polysaccharide-based nanostructures for cancer therapy

Conventional tumor chemotherapy faces limitations including drug resistance, high toxicity, non-selectivity, and side effects. Nano-drug delivery systems (DDSs) demonstrate stronger efficacy via enhanced permeability and retention (EPR) effect in tumor vasculature. This review provides a comprehensive analysis of a promising solution: redox-responsive drug delivery systems engineered from biocompatible polysaccharides. It exclusively details how the distinct reductive (glutathione, GSH) and oxidative (reactive oxygen species, ROS) species within the tumor microenvironment (TME) can be exploited for triggered drug release. We systematically evaluate a wide range of responsive groups - from established and emerging linkages such as disulfides, diselenides, thioketals, arylboronates, Pt (IV)- and ferrocene-based structures - integrated with versatile polysaccharide carriers. This review critically examines how these designs not only facilitate selective drug release and activation within tumor site but also enable active targeting (for instance via CD44 receptors) and synergistic combination therapies including photodynamic therapy (PDT) and immunotherapy. Furthermore, we discuss the key challenges in clinical translation and offer a perspective on integrating artificial intelligence for the design of personalized nanomedicines. This review by combining design approaches, their efficacy, and limitations assist scientists to select the optimal polysaccharide and most effective redox-responsive group to maximize anticancer effect and minimize off-target effects.