A unique approach using the large photoacoustic effect of single-walled carbon nanotubes (SWNTs) for targeting and selective destruction of cancer cells is demonstrated. SWNTs exhibit a large photoacoustic effect in suspension under the irradiation of a 1064-nm Q-switched millisecond pulsed laser and trigger a firecracker-like explosion at the nanoscale. By using such an explosion, a photoacoustic agent is developed by functionalizing the SWNTs with folate acid (FA) that can selectively bind to cancer cells overexpressing folate receptor on the surface of the cell membrane and kill them through SWNT explosion inside the cells under the excitation of millisecond pulsed laser. The uptake pathway of folate-conjugated SWNTs into cancer cells is investigated via fluorescence imaging and it is found that the FA-SWNTs can enter into cancer cells selectively with a high targeting capability of 17-28. Under the treatment of 1064-nm millisecond pulsed laser, 85% of cancer cells with SWNT uptake die within 20 s, while 90% of the normal cells remain alive due to the lack of SWNTs inside cells. Temperature changes during laser treatment are monitored and no temperature increases of more than +/- 3 degrees C are observed. With this approach, the laser power used for cancer killing is reduced 150-1500 times and the therapy efficiency is improved. The death mechanism of cancer cells caused by the photoacoustic explosion of SWNTs is also studied and discussed in detail. These discoveries provide a new way to use the photoacoustic properties of SWNTs for therapeutic applications.

The intracellular uptake and subcellular localization of carbon nanotubes strongly depend on the physical size of the materials. Multiwalled carbon nanotubes (MWNTs; 0.5–2 μm in length, 10–30 nm in diameter) are excluded from the interior of the cell; long single‐walled carbon nanotubes (L‐SWNTs) of length 100–200 nm (1–3 nm in diameter) are only internalized into cytoplasm, whereas short ones (S‐SWNTs) of length 50–100 nm partly reside in the cell nucleus.

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Herein we studied the uptake, trafficking and distribution of folate conjugated single walled carbon nanotubes (SWNTs) within living cells. SWNTs were noncovalently functionalized with chitosan and then linked with folate acid and fluorescence dye Alexa Fluor 488 (denoted FA-SWNTs). Hep G2 cells were cultured in vitro and incubated with FA-SWNTs at different levels. The FA-SWNTs exhibited a concentration-dependent uptake within Hep G2 cells, and Hep G2 cells were able to internalize FA-SWNTs via a folate receptor-mediated pathway. The distribution of nanotubes inside cells demonstrated that the FA-SWNTs only locate in the cytoplasm and not in nuclei, indicating the failure of transporting through the nuclear envelope. Transmission electron microscope (TEM) results showed the presence of FA-SWNTs in lysosomes and the discharge to extracellular space after incubation with nanotubes for 5 h. No obvious cellular death rate was observed when the concentration of nanotubes was below 50 µg ml(-1). However, cells with FA-SWNT uptake showed a concentration-dependent apoptosis. These discoveries might be helpful for understanding the interaction of SWNTs and living cells.