Natural polysaccharides and their derivatives targeting the tumor microenvironment: A review

Polysaccharides have gained attention as valuable supplements and natural medicinal resources, particularly for their anti-tumor properties. Their low toxicity and potent anti-tumor effects make them promising candidates for cancer prevention and treatment. The tumor microenvironment is crucial in tumor development and offers potential avenues for novel cancer therapies. Research indicates that polysaccharides can positively influence the tumor microenvironment. However, the structural complexity of most anti-tumor polysaccharides, often heteropolysaccharides, poses challenges for structural analysis. To enhance their pharmacological activity, researchers have modified the structure and properties of natural polysaccharides based on structure–activity relationships, and they have discovered that many polysaccharides exhibit significantly enhanced anti-tumor activity after chemical modification. This article reviews recent strategies for targeting the tumor microenvironment with polysaccharides and briefly discusses the structure–activity relationships of anti-tumor polysaccharides. It also summarises the main chemical modification methods of polysaccharides and discusses the impact of chemical modifications on the anti-tumor activity of polysaccharides. The review aims to lay a theoretical foundation for the development of anti-tumor polysaccharides and their derivatives.