An intelligent responsive nanoplatform based on a DNA nanoflowers/Mn:CuS hybrid for targeted and synergistic cancer therapy

Abstract

The development of intelligent nanoplatforms that integrate tumor targeting, stimuli-responsive drug release, and multimodal therapy remains a significant challenge for precise cancer treatment. Herein, a nanoplatform based on DNA nanoflowers and Mn:CuS nanoparticles with a unique architecture and multiple therapeutic functions was constructed. The DNA nanoflowers derived from rolling circle amplification (RCA) served as the scaffold, enabling the efficient intercalation of Mn:CuS nanoparticles and doxorubicin (DOX). Furthermore, the sgc-8 aptamer was incorporated into the DNA scaffold for specific recognition of HeLa cells. The intercalated Mn:CuS nanoparticles exhibited photothermal therapeutic activity, peroxidase (POD)/oxidase (OXD)-like properties and glutathione peroxidase (GPx)-like activity, thus achieving amplified therapeutic efficacy toward tumor cells. Moreover, the DOX release was demonstrated to be precisely controllable in acidic environments and under near-infrared (NIR) irradiation, which ensured tumor-specific drug release. Thus, synergistic chemotherapy, photothermal therapy and chemo-dynamic therapy (CDT) of cancers were achieved. Compared with the conventional single-function nanocarriers, this multifunctional hybrid system combines specific target recognition, responsive drug delivery, and multimodal therapeutic treatment, offering a promising avenue for precise and effective cancer therapy.