Biomedical Engineering Reference
In-Depth Information
6.2 Functionalized Carbon Nanotubes
Several drug delivery approaches have been carried out using carbon nanotubes
(CNTs) [ 53 - 55 ]. The biocompatibility of CNTs is a significant issue in many of
their proposed bio-applications. For the solubilization of CNTs, the attachment of
relatively large functional groups to the nanotubes is required because CNTs are
insoluble in water. The first report of CNT functionalization was reported by
Haddon and coworkers on the amidation of nanotube-bound carboxylic acids
with long-chain alkylamines, such as octadecylamine [ 56 ]. A variety of oligomeric
and polymeric compounds have been used in the functionalization of CNTs for their
solubility in common organic solvents and/or water.
Convenient and effective delivery of functionalized CNTs to a targeted site faces
several limitations. Nanocapsules have been proposed as drug carriers that could be
used to realize the “magic bullet” concept proposed by Nobel Prize winner Paul
Ehrlich (1854-1915). Paul Ehlrich [ 57 ] at the beginning of the twentieth century,
refers to a drug capable of targeting a particular site and releasing its contents when
desired. In order to accomplish this, novel polymeric membrane microcapsule CNT
devices have been developed for targeted delivery of therapeutics. CNTs were
encapsulated in an alginate-poly( L -lysine)-alginate (APA) membrane to form a
polymeric membrane targeted drug delivery device. The nanotubes were embedded
in the core or attached to the surface of different types of alginate capsules. The
device could be functionalized with targeting ligands for specific diseases or sites of
the system, along with the therapeutic moiety to improve the clinical efficiency.
The polymeric membrane protects the functionalized CNTs carrying the therapeu-
tics from the harsh external environments encountered during drug delivery. This
novel approach facilitates delivery of CNTs and their cargo safely and effectively to
target sites.
Folic acid-conjugated CNTs have been investigated for site-specific delivery of
drugs. Figure 11 shows an example of folate receptor-mediated targeting of
nanoparticles on cancer cell lines. Folate has been used as a targeting ligand
because of the presence of overexpressed folate receptors on many cancer cells
[ 58 , 59 ]. The ability of single-walled carbon nanotubes (SWNTs) attached to a
therapeutic agent (structure 1 in Fig. 10 ) to destroy cancer cells was studied by
using the MTT assay. Folate receptor-mediated targeting studies were carried out
on folate receptor-positive [FR(+)] human choriocarcinoma (JAR) and human
nasopharyngeal carcinoma (KB) cell lines. The uptake mechanism of folate-
mediated delivery of folate-conjugated CNTs is illustrated in Fig. 11 . The study
on CNTs as a vector for drug delivery into living cells was carried on HeLa cells
[ 60 ], as shown in Fig. 12 . HeLa cells were incubated with AlexaFluor594-labeled
SWNTs for 12 h at 37 C, and living cells were observed under confocal fluores-
cence microscope for a CNT uptake study as shown in Fig. 12a , which shows dual
confocal detection of AlexaFluor594-SWNT (red) internalized into cells, with the
membrane stained by AlexaFluor488 (green).
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