In this article, we used an artificial
DNA base to manipulate the formation of
DNA nanoflowers (NFs) to easily control their sizes and functionalities. Nanoflowers have been reported as the noncanonical self-assembly of multifunctional
DNA nanostructures, assembled from long
DNA building blocks generated by rolling circle replication (RCR). They could be incorporated with myriad functional moieties. However, the efficacy of these
DNA NFs as potential nanocarriers delivering cargo in biomedicine is limited by the bioavailability and therapeutic efficacy of their cargo. Here we report the incorporation of
metal-containing artificial analogues into
DNA strands to control the size and the functions of NFs. We have engineered bioinspired, size-controllable, self-degradable
cancer-targeting
DNA nanoflowers (Sgc8-NFs-Fc) via the incorporation of an artificial sandwich base. More specifically, the introduction of a
ferrocene base not only resulted in the size controllability of Sgc8-NFs-Fc from 1000 to 50 nm but also endowed Sgc8-NFs-Fc with self-degradability in the presence of H2O2 via Fenton's reaction. In vitro experiments confirmed that Sgc8-NFs-Fc/Dox could be selectively taken up by
protein tyrosine kinase 7 (PTK7)-positive
cancer cells and subsequently cleaved via Fenton's reaction, resulting in rapid release kinetics, nuclear accumulation, and enhanced cytotoxicity of their cargo. In vivo experiments further confirmed that Sgc8-NFs-Fc has good
tumor-targeting ability and could significantly improve the therapeutic efficacy of
doxorubicin in a xenograft
tumor model. On the basis of their tunable size and on-demand drug release kinetics upon H2O2 stimulation, the Sgc8-NFs-Fc nanocarriers possess promising potential in drug delivery.