Subcellular Tracking of Drug Release from Carbon Nanotube Vehicles in Living Cells

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 8; no. 5; pp. 777 - 782
• Main Authors: Kang, Bin, Li, Jun, Chang, Shuquan, Dai, Mingzhu, Ren, Chao, Dai, Yaodong, Chen, Da
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 12.03.2012; WILEY‐VCH Verlag
• Subjects: carbon nanotubes; Cells, Cultured; doxorubicin; Doxorubicin - chemistry; Drug Carriers - chemistry; drug delivery; drug release; Hydrogen-Ion Concentration; Microscopy, Confocal; Nanotubes, Carbon - chemistry; subcellular tracking
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201101714

The direct observation of drug release from carbon nanotube vehicles in living cells is realized through a unique two‐dye labeling approach. Single‐walled carbon nanotubes (SWNTs) are firstly marked with fluorescein isothiocyanate (FITC) to track their location and movement inside the cell. Then a fluorescent anticancer drug doxorubicin (DOX) is attached by means of π‐stacking onto SWNTs. Delivered by SWNTs into cells, DOX will detach from the vehicle in an acidic environment due to the pH‐dependent π–π stacking interaction between DOX and SWNTs. From observation of the two different kinds of fluorescence (green and red) that respectively represent the carrier SWNTs and drug DOX, the process of drug release inside the living cell can be monitored under a confocal microscope. Results show that the drug DOX detaches from SWNTs inside the lysosomes to yield free molecules and escape into the cytoplasm and finally into the nucleus, while the vehicle SWNTs are trapped inside the lysosomes, without entering the nucleus. The current observations confirm previously proposed mechanisms for drug/DOX release inside cells. The experimental establishment of drug‐release mechanisms in living cells here might provide important insights for future design of new drug‐delivery and release systems. The subcellular release of anticancer drug DOX from carbon nanotube vehicles in living cells is directly observed under a confocal microscope using a unique two‐dye labeling approach. Imaging clearly shows the time‐dependent process of drug transportation into cells and release to the cell nucleus. The drug DOX detaches from SWNTs inside the lysosomes to yield free molecules to escape into the cytoplasm and finally into the cell nucleus, while the vehicle SWNTs are trapped inside lysosomes, without entering the nucleus.