Multifunctional DNA Nanoplatform Based on CuInS/ZnS QDs and Rolling Circle Amplification for Synergistic PTT/CDT/CT of Multidrug Resistant Cancer Cells

Synergistic therapy holds significant potential in cancer diagnosis and treatment, yet faces substantial challenges such as nonspecific drug release and tumor multidrug resistance (MDR). Herein, we report a self-assembled DNA nanoplatform (ZCIS QDs@RD) based on CuInS/ZnS QDs (ZCIS QDs) and rolling circle amplification (RCA) for synergistic photothermal therapy (PTT)/chemodynamic therapy (CDT)/chemotherapy (CT). The nanoplatform achieved selective targeting of breast cancer cells by modifying the multivalent AS1411 aptamer. The hydrothermally synthesized ZCIS QDs exhibited excellent fluorescence properties, allowing for targeted imaging of cancer cells. Moreover, under 808 nm laser irradiation, ZCIS QDs demonstrated both photothermal conversion and peroxidase-like activity, thereby contributing to the synergistic therapeutic effects. Furthermore, the long single-stranded DNA generated via RCA offered high programmability, and its assembled structure (RA) served as an efficient carrier for codelivering doxorubicin (Dox) and antisense oligonucleotides (ASO). Under the action of deoxyribonucleases, controlled disassembly and sustained drug release were achieved, effectively reversing the MDR. Experimental results proved that ZCIS QDs@RD could not only identify cancer cells by fluorescence imaging but also realize PTT/CDT/CT multimode synergistic treatment, which provides a strategy for targeted cancer diagnosis and treatment.