Multiple-mRNA-controlled and heat-driven drug release from gold nanocages in targeted chemo-photothermal therapy for tumors

• Published in: Chemical science (Cambridge) Vol. 12; no. 37; pp. 12429 - 12436
• Main Authors: Zhang, Hao, Gao, Ze, Li, Xiaoxiao, Li, Lu, Ye, Sujuan, Tang, Bo
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 29-09-2021; The Royal Society of Chemistry
• Subjects: Cancer therapies; Chemistry; Doxorubicin; Drug carriers; Drug delivery systems; Fluorescence; Gold; Infrared radiation; Locks; Nanostructure; Porous walls; System effectiveness; Tumors
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d1sc02017j

Multifunctional drug delivery systems enabling effective drug delivery and comprehensive treatment are critical to successful cancer treatment. Overcoming nonspecific release and off-target effects remains challenging in precise drug delivery. Here, we design triple-interlocked drug delivery systems to perform specific cancer cell recognition, controlled drug release and effective comprehensive therapy. Gold nanocages (AuNCs) comprise a novel class of nanostructures possessing hollow interiors and porous walls. AuNCs are employed as a drug carrier and photothermal transducer due to their unique structure and photothermal properties. A smart triple-interlocked I-type DNA nanostructure is modified on the surface of the AuNCs, and molecules of the anticancer drug doxorubicin (DOX) are loaded as molecular cargo and blocked. The triple-interlocked nanostructure can be unlocked by binding with three types of tumor-related mRNAs, which act as "keys" to the triple locks, sequentially, which leads to precise drug release. Additionally, fluorescence-imaging-oriented chemical-photothermal synergistic treatment is achieved under illumination with infrared light. This drug delivery system, which combines the advantages of AuNCs and interlocked I-type DNA, successfully demonstrates effective and precise imaging, drug release and photothermal therapy. This multifunctional triple-interlocked drug delivery system could be used as a potential carrier for effective cancer-targeting comprehensive chemotherapy and photothermal therapy treatments.
Schematic illustration of the multiple-mRNA-controlled and heat-driven drug release from gold nanocages.