Abstract: Herein, a rolling circle amplification (RCA)-based assembly technique was proposed, which utilized the long single-stranded DNA produced by RCA as a scaffold. This scaffold was assembled with functional short strands into multivalent aptamers and subsequently combined with iron-doped red carbon dots (Fe-CDs) to construct a multivalent aptamer-based nanoplatform, termed AFD, for precision combination cancer therapy. In the AFD nanoplatform, the MUC1 aptamer exerted efficient targeting capabilities, precisely acting on cancer cells while minimizing collateral damage to normal cells. The Fe-CDs possessed peroxidase-like activity, which catalyzed the decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (?OH), thereby achieving chemodynamic therapy (CDT). Furthermore, the abundant CG base pairs within the AFD structure enabled the high-efficiency loading of doxorubicin (DOX). Upon entering cancer cells via highly efficient targeting, the multivalent aptamers released the encapsulated Fe-CDs and DOX, facilitating the effective eradication of cancer cells. In summary, this multivalent aptamer nanoplatform based on DNA and Fe-CDs provided a promising and highly selective approach for enhancing the efficacy of cancer treatment.

Key words: Rolling circle amplification, Carbon dots, Polyvalent aptamers, Drug delivery, Cancer therapy