We present a rolling circle amplification (RCA)-based
nanoplatform
that integrates dual-targeting, photothermal therapy (PTT), chemodynamic
therapy (CDT), gene therapy (GT), and chemotherapy (CT) for synergistic
breast cancer therapy. First, RCA-assembly (RA) was constructed by
integrating RCA and three single-stranded DNA (ssDNA) with different
functions (S2.2 aptamer chain, 17-E DNAzyme chain, and carboxyl chain).
Then, RA-Dox (RD) was further constructed based on the property of
doxorubicin (Dox) autonomously binding to G–C bases. Finally,
Fe3O4 NPs modified with citrate and polydopamine
nanoshell (CFO@PDA NPs) were loaded onto RD through an amidation reaction,
which was named CFO@PDA@RD. In vitro MCF-7 cell experiments demonstrated
that dual-targeting significantly enhanced the uptake of nanoplatform
by MCF-7 cells. The nanoplatform not only has excellent photothermal
performance but can also catalyze H2O2 to generate
hydroxyl radicals (•OH) in situ and consume reduced
glutathione (GSH) to diminish the antioxidant capacity of the tumor.
Degradation of the nanoplatform resulted in the release of Fe2+ for the activation of DNAzyme for the cleavage of miRNA-21
overexpressed in MCF-7 cells. In addition, the high loading and effective
release of Dox by nanoplatform further endowed the nanoplatform with
a chemotherapy effect. In summary, the CFO@PDA@RD nanoplatform with
a multimodal synergistic treatment effect has great potential in breast
cancer treatment.