Developing Fucose Grafted Dendrimers as a Biocompatible and Targeted System for the Delivery of Sinapic Acid

ABSTRACT Sinapic acid (SIP) is a plant‐derived chemotherapeutic agent with many pharmacological actions, including anticancer activity. However, SIP exhibits anticancer effects at very high doses due to its poor water solubility. Dendrimers, a novel class of nanopolymers, have been explored for improving the solubility of water‐insoluble phytochemicals. In the present work, PAMAM dendrimers (G4DD) were conjugated to fucose for developing a targeted nanocarrier (FUC‐G4DD) for the delivery of sinapic acids to human colon cancer cells (HCT116). Tumor cells overexpress sugar receptors on their cell surfaces and are an important target for cancer treatment. With the use of MALDI‐TOF mass spectroscopy, proton nuclear magnetic resonance, and infrared spectroscopy, the fucosylation of G4DD was verified. The FUC conjugation overcomes the non‐specific toxicity of G4DD. The SIP was formulated with FUC‐G4DD for amplifying the aqueous solubility and anticancer efficacy of SIP up to 6.5 times and 4 times, respectively. Cellular uptake results supported higher uptake of SIP–FUC–G4DD by colon cancer cells through the process of receptor‐mediated endocytosis, and it could be the reason for high anticancer efficacy, induction of apoptosis, and inhibition of colony formation in HCT116 cells after treatment with SIP–FUC–G4DD as compared to SIP. FUC‐G4DD also aided in improving the stability, dissolution, and release behavior of SIP. Thus, fucosylated dendrimers have been designed for targeted drug delivery to SIP with higher anticancer activity in the treatment of colon cancer.