Design and Development of Theranostic Nanomedicines - Nanotechnology for Biomedical Imaging and Diagnostics - page 429

uptaken by cells through endocytosis. With appropriate surface coatings, CnTs
have been reported to be internalized by cells through endocytosis [64]. even
though the detailed mechanism behind the uptake remains unclear, this feature
allows CnTs to deliver drug molecules to cells without the need of targeting
molecules. Due to the ease of functional group introduction to CnTs' surface,
targeting molecules can also be attached to CnTs through bioconjugation chem-
istry. For example, peptides and antibodies have been attached to CnTs and
evaluated in tumor-targeted in vivo imaging with photoacoustic and raman
imaging [65, 66].
CnTs are developed based on graphene, which is inert and inhibitive to most
conjugation chemistry. To introduce hydrophilicity and functionality to CnTs,
extreme oxidative conditions can be applied to create defects on CnT surface where
polar and functional groups can be mounted. one method developed by Dai's group
involves refluxing sWCnTs in nitric acid for two 36-h periods separated by sonica-
tion for 30 min [67]. Multiple carboxyl groups are then generated on the surface,
making sWCnTs water soluble and functional. pegylated phospholipids are often
introduced to the sWCnT surface to improve stability and biocompatibility as well
as lengthen circulation time.
although sWCnTs have intense nir absorption, the molar extinction coefficients
are lower than those of gnps. in an effort to improve the absorption, Kim et al . devel-
oped gold-plated sWCnTs, which showed a 100-fold enhancement in photoacoustic
signal [68]. golden nanotubes were synthesized by coating a 4-8 nm-thick gold layer
onto a sWCnT core with a diameter of 1.5-2 nm. These golden nanotubes are highly
water soluble, well dispersed, relatively uniform in size, and rod shaped with average
dimensions of 100 nm in length and 11 nm in diameter [68].
The strong nir absorbance of CnTs has been utilized to treat tumor through
pTT in cancer mouse models. it was demonstrated that nir irradiation of pegylated
sWCnTs led to complete destruction of tumors in a human epidermoid mouth
carcinoma mouse model [69]. no harmful side effects or recurrence of tumors
were observed over 6 months after treatment, whereas tumors in control groups
continued to grow. In vivo therapeutic studies using anticancer drug-loaded CnTs
have also been reported. in a 4T1 breast cancer mouse model, sWCnT-pTX
conjugate afforded much longer blood circulation time than pTX due to the
pegylated surface of sWCnTs [61]. This led to high tumor uptake and treatment
efficacy. The pTX on sWCnT was likely released via cleavage of the ester bond
between pTX and sWCnT by esterase. Bhirde et al . reported the first targeted
in vivo therapeutic study using multifunctional sWCnT bioconjugates [70]. The
two bioconjugates (sWnT-quantum dots (Qdot)-epidermal growth factor (egF)
and sWnT-cisplatin-egF) have several components including egF as the target-
ing molecule, cisplatin as the anticancer drug, Qdot as the fluorescence imaging
moiety, and sWnT as the carrier. In vivo imaging showed that sWnT-Qdot-egF
injected into live mice was selectively taken up by tumors. Moreover, regression
of tumor growth was rapid in mice treated with sWnT-cisplatin-egF relative to
nontargeted sWnT-cisplatin.