Dual covalent functionalization of singlewalled carbon nanotubes for effective targeted cancer therapy
Publication Type
Original research

Chemotherapy is a mainstay strategy in the management of cancer. Regrettably, current
chemotherapeutic agents are cytotoxic not only to cancer cells but also to healthy cells,
resulting in dose-limiting serious side effects. Therefore, many researchers are eager to
develop new drug delivery systems that may help to decrease the side effects and the target
delivery of chemotherapy to cancer cells. One of the epochal drug delivery systems in this field
is based on carbon nanotubes technology. The aim of this work is the dual covalent
functionalization of single-walled carbon nanotubes (SWCNTs) with doxorubicin (DOX)
connected with acid-labile linkage and mannose (Man) as a targeting agent. The
characterization of the developed nano-drug by transmission electron microscopy showed
good dispersibility of the functionalized SWCNTs with diameters (6–10) nm. Moreover, the
percentage of functionalization was determined by thermogravimetric analysis showing 25%
of functionalization in the case of SWNCTs-NHN-DOX (7) and 51% for SWCNTs-Man-
NHN-DOX (11). The in vitro release profile of Dox from SWNCTs-NHN-DOX (7) showed
45% of the loaded drug was released over 18 h at pH 7.4 and almost complete release at pH 6.4
at 37 °C. However, the in vitro release profile of Dox from SWCNTs-Man-NHN-DOX (11)
showed 75% of the loaded drug was released over 5 h at pH 6.4 at 37 °C. The cytotoxic effect
of the compounds was studied on liver cancer cells (HepG2) at different concentrations and
different pH conditions and was compared with DOX alone. The cytotoxicity of compounds
SWCNTs-NHN-DOX (7) and SWCNTs-Man-NHN-DOX (11) was enhanced at pH 6.5, where
the cell viability in both test compounds was significantly reduced by almost 50% compared to
the cell viability at pH 7.4 for the same test compound Moreover, the pre-incubation of cells
with different concentrations of mannose reduced the cytotoxicity of compound (11) by more
than 50%, suggesting that the entry of this complex could be at least in part facilitated by
mannose receptors, which imparts this complex a kind of selectivity for cancer cells that
overexpress this type of receptors.

Publisher Country
United Kingdom
Thomson Reuters
Impact Factor
Publication Type
Both (Printed and Online)