Efficient co-delivery of microRNA 21 inhibitor and doxorubicin to cancer cells using core–shell tecto dendrimers formed via supramolecular host–guest assembly

Abstract

Development of versatile and powerful nanoplatforms for efficient therapeutic delivery represents a major topic for current nanomedicine. Herein, we present the development of core–shell tecto dendrimers (CSTDs) for co-delivery of a therapeutic gene and drug for enhanced anticancer therapy applications. In this work, CSTDs were first prepared via supramolecular recognition of β-cyclodextrin (CD)-decorated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers as cores and adamantane (Ad)-functionalized G3 PAMAM dendrimers as shell components. The formed CSTDs with each G5 dendrimer surrounded with 4.2 G3 dendrimers were evaluated as a gene vector for delivery of plasmid DNA encoding enhanced green fluorescent protein as well as microRNA 21 inhibitor (miR 21i). We show that under an appropriate N/P ratio, the CSTDs enable effective transfection of both genetic materials to cancer cells. In particular, the transfection of miR 21i led to the inhibition of cancer cell migration, decreased miR 21 gene expression, and the effective regulation of the target genes and proteins (e.g., PTEN, PDCD4, p53, and Caspase-3). Furthermore, we revealed that the CSTDs were able to co-deliver miR 21i and an anticancer drug doxorubicin, leading to enhanced therapeutic efficacy to cancer cells in vitro. Our findings imply that the developed CSTDs could be adopted as a versatile platform for effective co-delivery of different therapeutic components for enhanced anticancer therapy applications.