Encapsulation of doxorubicin within multifunctional gadolinium-loaded dendrimer nanocomplexes for targeted theranostics of cancer cells

Abstract

We report the use of multifunctional gadolinium-loaded dendrimer nanocomplexes to encapsulate an anticancer drug doxorubicin (DOX) for magnetic resonance (MR) imaging and chemotherapy of cancer cells. In this study, amine-terminated generation five poly(amidoamine) dendrimers (G5.NH₂) were modified with chelator/gadolinium (Gd) complexes and folic acid (FA) via a polyethylene glycol (PEG) spacer, followed by acetylation of the remaining dendrimer terminal amines. The thus formed G5.NHAc–DOTA(Gd)–PEG–FA complexes were used to encapsulate DOX within the dendrimer interior. We show that the G5.NHAc–DOTA(Gd)–PEG–FA/DOX complexes having 8.5 DOX molecules and DOTA/Gd complexes per dendrimer are stable under different pH conditions, and are able to release DOX in a sustained manner. The FA modification enables efficient targeting of the particles to cancer cells overexpressing FA receptors (FAR), and thus effective targeted MR imaging of the cancer cells in vitro. Likewise, the encapsulation of DOX within the dendrimer/Gd complexes does not compromise the therapeutic efficacy of the DOX drug. Importantly, by virtue of the FA-directed targeting, the formed multifunctional dendrimeric nanocomplexes are able to exert specific therapeutic efficacy of DOX to the FAR-overexpressing cancer cells in vitro. The developed multifunctional dendrimers with both MR imaging agents Gd(III) complexed via the conjugated chelator and anticancer drug physically encapsulated within the dendrimer interior may hold great promise to be used as a theranostic nanoplatform for targeted MR imaging and chemotherapy of different types of cancer.