Abstract
The development of cost-effective targeted drug delivery systems for cancer chemotherapy still remains a great challenging task. Here, we describe the synthesis and characterization of multifunctional polyethylenimine (PEI) as an effective vehicle to load an anticancer drug doxorubicin (DOX) for in vivo targeted cancer therapy. In this study, PEI was sequentially conjugated with polyethylene glycol (PEG) monomethyl ether, PEGylated folic acid (FA), and fluorescein isothiocyanate (FI). This was followed by the acetylation of the remaining PEI surface amines. The formed FA-targeted multifunctional PEI (FA-mPEI) was used as a vehicle to encapsulate DOX. We show that the formed FA-mPEI/DOX complexes with each PEI encapsulating 6.9 DOX molecules are water dispersible and can sustainably release DOX in a pH-dependent manner, showing a higher release rate under acidic pH conditions than under physiological pH conditions. Furthermore, the complexes display specific therapeutic efficacy to cancer cells in vitro and a subcutaneous tumor model in vivo, and have good organ compatibility. The designed multifunctional PEI may be used as an effective vehicle for targeted cancer chemotherapy.
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