Covalent functionalization of SWCNT with combretastatin A4 for cancer therapy

Single walled carbon nanotubes (SWCNT) are currently under intensive investigation by many
labs all over the world for being promising candidates for cancer chemotherapy delivery. On the
other hand, combretastatin A4 (CA4) is an anticancer drug that induces cell apoptosis by
inhibiting tubulin polymerization. However, it has the disadvantage of low water solubility and
the non-selective targeting. Therefore, we aim to create nano-drug from the functionalization of
SWCNT covalently with CA4 through click reaction in the presence of tetraethylene glycol
linker in order to improve its dispersibility. Scanning electron microscopy and transmission
electron microscopy showed good dispersibility of the functionalized SWCNT with diameters of
5–15 nm. Moreover, thermogravometric analysis showed that the efficiency of SWCNT
functionalization was around 45%. The in vitro release profile of CA4 at physiological
conditions showed that approximately 90% of the loaded drug was released over 50 h. After that MTS test was used to determine the suitable concentration range for the in vitro investigation of the SWCNT-CA4. After that the cytotoxic activity of the SWCNT-CA4 was evaluated by flow cytometry using annexin V/propidium iodide (PI) test. In comparison with free CA4, SWCNTCA4 treatment demonstrated a significant increase in necrotic cells (around 50%) at the expense of the proportion of the apoptotic cells. Moreover, cell cycle PI test demonstrated that free CA4 and SWCNT-CA4 caused G2/M arrest. However with CA4 treatment higher proportion of cells were in the S-phase while with SWCNT-CA4 treatment greater proportion of cells appeared to be in the G1-phase. Taken together, the provided data suggest that the novel SWCNT-CA4 has a significant anticancer activity that might be superior to that of free CA4.

IOP science
Publisher Country
United States of America
Thomson Reuters
Impact Factor
Publication Type
Both (Printed and Online)