Telomerase-activated Au@DNA nanomachine for targeted chemo-photodynamic synergistic therapy

• Published in: MedChemComm 2023-11, Vol.14 (11), p.2268-2276
• Main Authors: Zhou, Yun-Jie, Zhang, Jing, Cao, Dong-Xiao, Tang, An-Na, Kong, De-Ming
• Format: Article
• Language: English
• Subjects: Antitumor agents; Aptamers; Cancer; Cell surface; Chemotherapy; Deoxyribonucleic acid; DNA; Photodynamic therapy; Telomerase; Tumors
• ISSN: 2632-8682; 2040-2503; 2632-8682; 2040-2511
• DOI: 10.1039/d3md00379e

We successfully designed a smart activatable nanomachine for cancer synergistic therapy. Photodynamic therapy (PDT) and chemotherapy can be activated by intracellular telomerase while anti-cancer drugs can be effectively transported into tumour cells. An Sgc8 aptamer was designed, which can specifically distinguish tumour cells from normal cells and perform targeted therapy. The nanomachine entered the tumour cells by recognising PTK7, which is overexpressed on the surface of cancer cells. Then, the "switch" of the system was opened by TP sequence extension under telomerase stimulus. So, the chemotherapeutic drug DOX was released to achieve the chemotherapy, and the Ce6 labelled Sgc8-apt was released to activate the PDT. It was found that if no telomerase existed, the Ce6 would always be in an "off" state and could not activate the PDT. Telomerase is the key to controlling the activation of the PDT, which effectively reduces the damage photosensitisers cause to normal cells. Using in vitro and in vivo experiments, the nanomachine shows an excellent performance in targeted synergistic therapy, which is expected to be utilised in the future. An intelligent activated nanomachine for collaborative cancer therapy has been successfully designed. The nanomachine shows an excellent performance for the targeted synergistic therapy, which is expected to be utilized in clinical applications.