Zerumbone delivery to tumor cells via pH-sensitive polymeric micelles

This study aimed to develop a smart drug delivery system for zerumbone as an anticancer agent, to enhance its therapeutic efficacy against tumors. To this purpose, pH-sensitive polymer PEG-P(Asp-Hyd-Zer) was prepared by conjugating zerumbone to the side chain of the copolymer PEG-P(Asp-Hyd) via an acid-labile hydrazone bond. The resulting micelles were prepared in an aqueous solution with the size of 60 nm in diameter. The zerumbone pH-sensitive micelles remained stable at physiological pH = 7.4 but could be degraded in the acidic environment of endosomal/lysosomal compartments (pH < 6.0), allowing for targeted delivery of zerumbone to tumor cells. The release of zerumbone from the zerumbone pH-sensitive micelles was controlled by pH of the medium, with faster release observed under acidic conditions. In vitro and in vivo tests demonstrated that these zerumbone pH-sensitive micelles effectively induced cancer cell destruction under weakly acidic tumoral conditions, highlighting their potential as an effective delivery system for zerumbone. This synthesis method has potential applications in medicine for targeted drug delivery, especially for cancer treatments involving avascular tumor tissue.