Progress on hydroxyethyl starch-based smart nanomedicines

In recent years, hydroxyethyl starch (HES), a semi-synthetic polysaccharide with outstanding biodegradability, biocompatibility, and abundant modifiable sites, has emerged as a promising carrier in nanomedicine. This review systematically elaborates on the research advances of HES-based drug delivery systems, including HES-drug conjugates, block copolymers, stabilizers, and biomacromolecule conjugates. In biomedical applications, HES-based smart nanomedicines demonstrate unique advantages in cancer treatment including modulating tumor mechanical microenvironment (TMME), eliminating cancer stem cells (CSCs), and boosting immunotherapy, as well as in treating inflammatory bowel disease, stroke, and skin disinfection, by virtue of their targeted delivery and microenvironment-responsive properties. While HES offers notable advantages over traditional carriers such as polyethylene glycol (PEG) in terms of biocompatibility and cost, challenges remain in optimizing targeted delivery and precise release systems. Existing studies underscore the promising clinical translation potential of HES-based nanomedicines, positioning them as pivotal platforms for future precision therapy and diverse biomedical applications. • This article systematically summarizes the latest research advances in hydroxyethyl starch (HES)-based smart nanomedicines. • According to the distinct roles of HES in drug delivery systems, they are categorized into four major types: HES-drug conjugates, HES block copolymers, HES as stabilizers, and HES-biomacromolecule conjugates. • The applications of HES-based smart nanomedicines in cancer therapy and other biomedical fields are systematically introduced.