Synthesis of Folate Functionalized Biodegradable Amphiphilic Dendrimer-Like Star Polymer for Targeted Cancer Cells

Targeted drug delivery has attracted much attention due to their high efficacy and low side effects. In this work, well-defined poly(L-lactide) (PLLA) star polymer was synthesized by ring opening polymerization of L-lactide and a polyester dendron based on 2,2-bis(hydroxymethyl) propionic acid (bis-MPA) was prepared via a divergent method. A biodegradable dendrimer-like star polymer (DLSP) was formed by coupling of the PLLA star polymer and bis-MPA-based dendron. The surface groups of the DLSP were modified with carboxylic acid groups which were further reacted with amino-functionalized folic acid (FA) and triethylene glycol (TEG) to afford the folate-DLSP hybrid as a carrier for targeted drug delivery. All chemical structures were characterized by ¹H NMR and size exclusion chromatography (SEC) techniques. This folate-DLSP hybrid can form unimolecular micelles in aqueous solution and the micelle size was determined by dynamic light scattering (DLS). Doxorubicin (DOX), a hydrophobic anticancer drug, was encapsulated into the folate-DLSP micelles and the release of the encapsulated DOX was detected by UV–vis spectrophotometer. Flow cytometry analysis revealed that cellular uptake of DOX loaded folate-DLSP micelles against KB cells was much higher than that of the DOX loaded DLSP (without FA) micelles, thereby providing higher cytotoxicity. All these results indicated that the folate-DLSP micelles have great potential application in targeted drug delivery.