Synthesis of Biocompatible Cholesteryl-Carboxymethyl Xylan Micelles for Tumor-Targeting Intracellular DOX Delivery.

Patients with cancer suffer from severe side effects and reduced life quality, as chemotherapeutic drugs are cytotoxic toward normal cells as well as toward cancer cells. In recent years, nanoparticles have been explored as targeted drug delivery systems; however, problems such as toxicity and instability prevent their practical application. Here, we report the synthesis of cholesteryl-carboxymethyl xylan (CCMX) via an esterification reaction between the carboxyl group of carboxymethyl xylan and the hydroxyl group of cholesterol to form biocompatible micelles as a vehicle for targeted drugs. With its critical micelle concentration (CMC) depending on the degree of substitution (DS) of cholesteryl and ranging from 0.0024 to 0.017 mg/mL, CCMX could self-assemble and form nanoscale micelles in aqueous media. Taking doxorubicin (DOX) as a model drug, the drug encapsulation efficiency (EE%) of CCMX-3 (DS of 0.35 for cholesteryl) reached 91.3%, and this system exhibited excellent internalization ability, as verified by tumor cellular uptake tests. The results of in vitro cytotoxicity and in vivo antitumor activity tests of nude mice demonstrated that CCMX-3/DOX micelles effectively suppressed the growth of tumor cells by maintaining the cytotoxicity of commercial DOX injection while reducing the toxicity against normal cells and increasing the survival time.