Dual-Targeting Nanoplatform Based on Rolling Circle Amplification for Enhanced Multimodal Synergistic Treatment of Breast Cancer

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.