Sialic acid-modified docetaxel cationic liposomes: double targeting of tumor-associated macrophages and tumor endothelial cells

Taxane drugs are clinically used for the treatment of many types of cancers due to their excellent antitumor effects. However, the surfactants contained in the injections currently used in the clinic may have serious toxic side effects on the organism, making it necessary to develop new dosage forms. Cationic liposomes have been widely used in antitumor research because of their advantage of preferentially targeting tumor neovascularization, but antitumor by targeting tumor vasculature alone does not necessarily provide good results. Malignant tumors represent complex ecosystems, tumor-associated macrophages (TAMs) and tumor endothelial cells (TECs) in the tumor microenvironment play crucial roles in tumor growth. Therefore, given the ability to achieve active targeting of TAMs and TECs by using sialic acid (SA) as a targeting material, the potential of cationic nanoformulations to preferentially target neovascularization at the tumor site, and the excellent antitumor effects of the taxane drugs docetaxel (DOC), in the present study, sialic acid-cholesterol coupling (SA-CH) was selected as a targeting material to prepare a DOC cationic liposome (DOC-SAL) for tumor therapy. The results of the study showed that DOC-SAL had the strongest drug accumulation in tumor tissues compared with the common DOC formulations, and was able to effectively reduce the colonization of TAMs, inhibit the proliferation of tumor cells, and have the best tumor-suppressing effect. In addition, DOC-SAL was able to improve the internal microenvironment of tumors by modulating cytokines. In summary, this drug delivery system has good anti-tumor effects and provides a new option for tumor therapy.