Advances in research of hyaluronic acid modified nanomicelles for targeting tumor therapy and drug release behavior

Hyaluronic acid, also called hyaluronan(HA)is a biocompatible and biodegradable linear polysaccharide which is of interest for tumor targeting through cell surface CD44 receptors. It is widely applied in the field of tumor therapy as an anticancer drug delivery carrier, and has become a hot spot in the research of tumor targeted drug delivery system. In tumor drug therapy, the key to reduce toxicity is to actively target tumors by using anatomical, pathophysiological and microenvironmental differences between malignant tumors and normal tissues. Differentiation cluster 44(CD44)is a high-affinity receptor for HA, which can be marked as a tumor marker or a targeting receptor because it is overexpressed in tumor cells. The overexpression of CD44 receptors was observed in many tumors such as breast cancer, colorectal cancer, liver cancer and pancreatic cancer. The effect of hyaluronic acid drug nanocarriers on various tumors is briefly described, indicating that the overexpression of CD44 receptor is an ideal choice for the treatment of hyaluronic acid-based drug carriers. The CD44 ligand can increase the affinity of the nanocarrier for tumor cells by binding to the nano drug carrier. The HA structure is known for its potent tumor targeting effect due to the inclusion of CD44 ligand, which enhances uptake of tumor cells by the HA-CD44 receptor-mediated endocytosis pathway. The study reviewed the progression of hyaluronic acid nanomicelles in clinical tumor therapy and its release behavior. The percentage of drug release and release rate are the key factors in the overall efficacy of the treatment strategy. Therefore, a great number of studies have focused on inducing drug release in Cytosol by taking advantage of the difference between the internal and external environments of nanostructured micelles or through external stimulation post-treatment applications. The study proved that an acid environment is more favorable to achieve a greater release and drugs can be quickly and completely released in an oxygen-deficient environment. In addition, the great potential of hyaluronic acid nanomicelles in tumor therapy was also further identified in this article. In vitro and in vivo experimental studies have repeatedly shown that hyaluronic acid-based nanomicelles are a drug- and gene-specific targeting tumor delivery method, in combination with passive targeting, this active targeting strategy is a promising approach to providing chemotherapy drugs to CD44 overexpressing tumors. In conclusion, hyaluronic acid-based nanomicelles are biologically safe with great potential to drug release, blood compatibility and systemic tumor targeting which all implied it has good application prospects in clinical tumor treatment.