Targeted delivery of doxorubicin into cancer cells using a folic acid–dendrimer conjugate

We report here a general approach to using multifunctional poly(amidoamine) (PAMAM) dendrimer-based platform to encapsulate an anticancer drug doxorubicin (DOX) for targeted cancer therapy. In this approach, generation 5 (G5) PAMAM dendrimers modified with fluorescein isothiocyanate (FI) and folic acid (FA) via covalent conjugation, and with remaining terminal amines being acetylated (G5.NHAc-FI-FA) were used to complex DOX for targeted delivery of the drug to cancer cells overexpressing high-affinity folic acid receptors (FAR). We show that the formed G5.NHAc-FI-FA/DOX complexes with each dendrimer encapsulating approximately one DOX molecule are water soluble and stable. In vitro release studies show that DOX complexed with the multifunctional dendrimers can be released in a sustained manner. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell viability assay in conjunction with cell morphology observation demonstrates that the G5.NHAc-FI-FA/DOX complexes can specifically target and display specific therapeutic efficacy to cancer cells overexpressing high-affinity FAR. Findings from this study suggest that multifunctional dendrimers may be used as a general drug carrier to encapsulate various cancer drugs for targeting therapy of different types of cancer.