Biomedical Engineering Reference
In-Depth Information
blot analysis revealed an up-regulation of tumor suppressor gene p53 in HepG2
cell line. Intracellular ROS production in C-dots treated HepG2 cells increased
18.2-fold with respect to normal cells ultimately leading to apoptosis.
Apart from the use of C-dots for gene delivery, there have been reports on the
use of C-dots for anti-cancer drug delivery. Hollow C-dots (HCDs) have been
used for delivery of doxorubicin (DOX). The DOX-HCD drug delivery sys-
tem displayed a pH-dependent release and performed the dual role of cell imag-
ing and anti-cancer therapy. The inherent green fluorescence of HCDs and red
fluorescence of DOX formed a dual emission delivery system. Internalization of
such a system was observed on A549 cancer cells by fluorescence microscopy.
Green emission of HCDs in cytoplasm was observed after 24 h and red emission
inside nucleus was due to the release of DOX from HCD and its entry inside the
nucleus (Wang et al. 2013). Similarly, folic acid (FA) capped C-dots modified
with BSA have been used for the delivery of DOX to cancer cells. fC-dots-FA-
@DOX complex specifically targeted HeLa cancer cells and showed bright green
coloured fluorescence, where as bare C-dots without FA depicted negligible flu-
orescence in HeLa cells. fC-dots-FA-@DOX complex had an IC50 value of less
than 0.04 mM, much lower than free DOX (0.08 mM) due to enhanced targeting
and uptake by HeLa cells (Mewada et al. 2014). C-dots have also been integrated
with Oxaliplatin (CD-Oxa) by means of condensation reaction between the amino
groups on the surface of C-dots and the carboxyl group of Oxa(IV)-COOH. The
theranostic complex CD-Oxa combines the bioimaging properties of C-dots and
anti-cancer action of Oxaliplatin on a single platform. This allows the tracking
of drug molecules inside the cell by monitoring the fluorescence intensity of the
complex. The activity of CD-Oxa complex was tested against HepG2 cancer cells.
Upon incubation, the cells displayed multicolour emission due to internalization
of CD-Oxa. In vitro MTT assay was used to test the toxicities of oxaliplatin. IC
50 value of CD-Oxa on HepG2 cells was 3.4
ΚΌ
g/mL. Further, for in vivo studies
mouse were injected with CD-Oxa (0.72 mg/mL) at the site of tumor. The fluores-
cence emission was detected readily, fluorescence area spreaded around the injec-
tion site to form a gradient density distribution. Fluorescence signal faded after
24 h and subsequent injection was done. With increasing time, tumor suppression
was observed resulting in flattening of tumor area (Zheng et al. 2014). For C-dot
based photoresponsive theranostics, a quinoline phototrigger conjugated antican-
cer drug, 7-(3-bromopropoxy)-2-quinolylmethyl chlorambucil (Qucbl) was teth-
ered onto the surface of C-dots (Qucbl-Cdots) for photoresponsive and regulated
drug release. Their activity and cellular uptake was studied using HeLa cancer
cells. After 4 h incubation, cells exhibited bright green fluorescence in the cyto-
plasm and nucleus. Further, the cytotoxicity studies of Qucbl-Cdots on HeLa cells
depicted decrease in cell viability with an increase in chlorambucil concentration,
while the viability remain unaffected for C-dots treated cells. Exposure to light
caused the release of chlorambucil from Qucbl-Cdots inside the cells ultimately
leading to cell death. Optimal irradiation time for drug release to achieve the high-
est cytotoxicity was found to be 30 min, indicating the release of most of the teth-
ered drug from Qucbl-Cdots complex (Karthik et al. 2013).
