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)-O-center dot) 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.