NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy

• Published in: Journal of nanobiotechnology Vol. 21; no. 1; p. 186
• Main Authors: Li, Mengyue, Yang, Geng, Zheng, Yue, Lv, Jiazhen, Zhou, Wanyi, Zhang, Hanxi, You, Fengming, Wu, Chunhui, Yang, Hong, Liu, Yiyao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 10-06-2023; BioMed Central; BMC
• Subjects: Animals; Antimitotic agents; Antineoplastic agents; Apoptosis; Aptamers; AS1411 aptamer; Bcl-2 protein; Biocompatibility; Breast cancer; Cancer; Cancer therapies; Caspase-3; Cell death; Cell Line, Tumor; Chemotherapy; Controllability; Deoxyribonucleic acid; DNA; DNA - therapeutic use; DNA origami; Dosage and administration; Doxorubicin; Drug Delivery Systems - methods; Drug Liberation; Drugs; Endocytosis; Endosomes; FDA approval; Fluorescence; Health aspects; Hydrogen-Ion Concentration; Hyperthermia, Induced - methods; I.R. radiation; Imaging-guided therapy; Infrared lasers; Irradiation; Lasers; Light therapy; Lysosomes; Mice; Nanomaterials; Nanoparticles - therapeutic use; Near infrared radiation; Neoplasms - diagnostic imaging; Neoplasms - drug therapy; Nucleolin; Patient outcomes; Pharmacology; Phototherapy; Phototherapy - methods; Photothermal therapy; Proteins; Side effects; Toxicity; Tumor cells; Tumors; China; United States > US; Photothermal therapy; Chemotherapy; AS1411 aptamer; DNA origami; Imaging-guided therapy
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-01953-9

Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier's endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.