Photothermolysis of glioblastoma stem-like cells targeted by carbon nanotubes conjugated with CD133 monoclonal antibody

CD133+ cells in glioblastoma (GBM) display cancer stem cell-like properties and have been considered as the culprit of tumor recurrence, justifying exploration of potential therapeutic modalities targeting CD133+ cancer stem-like cells (CSCs). For photothermolysis studies, GBM-CD133+ and GBM-CD133– cells mixed with various ratios were challenged with single-walled carbon nanotubes (SWNTs) conjugated with CD133 monoclonal antibody (anti-CD133) and then irradiated with near-infrared laser light. Results show that GBM-CD133+ cells were selectively targeted and eradicated, whereas GBM-CD133– cells remained viable. In addition, in vitro tumorigenic and self-renewal capability of GBM-CD133+ treated with localized hyperthermia was significantly blocked. Furthermore, GBM-CD133+ cells pretreated with anti-CD133-SWNTs and irradiated by near-infrared laser 2 days after xenotransplantation in nude mice did not exhibit sustainability of CSC features for tumor growth. Taken altogether, our studies demonstrated that anti-CD133-SWNTs have the potential to be utilized as a thermal-coupling agent to effectively target and destroy GBM CSCs in vitro and in vivo.From the Clinical EditorGlioblastoma remains one of the most notorious cancer from the standpoint of recurrence and overall resistance to therapy. CD133+ stem cells occur among GBM cells, and may be responsible for the huge recurrence risk. This paper discusses a targeted elimination method of these cells, which may enable more efficient therapy in an effort to minimize or prevent recurrence.

Graphical AbstractAfter (a) GBM-CD133– and (b) GBM-CD133+ cells incubated separately with single-walled carbon nanotubes (SWNTs) tagged with CD133 monoclonal antibody (anti-CD133-SWNTs) for 6 h, 808-nm near-infrared (NIR) laser light was harnessed to irradiate both cell types. After washed with phosphate buffered saline (PBS) and stained with calcein-AM dye, fluorescent images of cells were taken. The GBM-CD133– cells located in the laser-shining zone remained viable with green fluorescence. However, the GBM-CD133+ cells located in the laser-shining region did not reveal green fluorescence (i.e., cell necrosis). To clarify the feasibility of selectively eradicating GBM-CD133+ cells by anti-CD133-SWNTs, a mixture of GBM-CD133+ and GBM-CD133– cells (1:1 ratio) was treated with anti-CD133-SWNTs for 6 h, washed with PBS, and then exposed to NIR laser. The image of (c) was no longer dark like (b), instead sparkling green fluorescence was visualized. This indicated that there were viable GBM-CD133– cells emitting green fluorescence in the NIR laser-shining zone; however, the equally mixed GBM-CD133+ cells were specially targeted by anti-CD133-SWNTs and thermally ablated by NIR laser.Figure optionsDownload high-quality image (109 K)Download as PowerPoint slide