Biomedical Engineering Reference
In-Depth Information
dendrimer exterior termini and contrast agents can either be conjugated with the
peripheral groups or can be resided in the core (Longmire et al. 2008). Two classes
of dendrimers with MR imaging proficiencies include: dendrimers incorporating
gadolinium (Gd) chelates and magneto-dendrimers (i.e. dendrimers containing
paramagnetic iron oxide particles).
Dendrimer based MRI agents offer better relaxivity and increased circula-
tion times than conventional low molecular weight (LMW) contrast agents such
as Gd-DTPA (DTPA
=
diethylenetriaminepentaacetic acid) and Gd-DOTA
(DOTA
=
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Gd-based
dendrimer agents for MRI are 'positive' contrast agents as compared to iron
oxide-based agents which produce a differential enhancement by signal reduction
(Barrett et al. 2009). Chiral dendrimer-triamine-coordinated Gd complexes as con-
trast agents for MRI imaging offer longitudinal relaxivity (r1) 3 times higher than
that of clinically used Gd-DTPA (Miyake et al. 2012). PEGylated Gd-loaded den-
drimer-entrapped gold nanoparticles (Gd-Au-DENPs) with two radiodense imag-
ing elements AuNPs and Gd(III) in a single system display both CT/MR imaging
capabilities with increased circulation times. They were able to image heart, liver,
kidney, and bladder of rat or mouse within a time frame of 45 min (Wen et al.
2013). Chen et al. (2013) developed folic acid (FA) conjugated-Gd-Au-DENPs as
nanoprobes for targeted CT/MR imaging of cancer cells. Lactobionic acid (LA)-
modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) have been used
for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma.
LA-Au DENPs imaging probes were injected both intravenously and intraperito-
nealy to the mice (Fig.
8
). The results suggested that the tumor CT values of the
targeted group injected with LA-Au DENPs was much more than the nontargeted
group at same time points. Additionally, intravenous injection enabled much more
sensitive CT imaging of the tumor model compared to intraperitoneal injection
(Liu et al. 2014).
Biodegradable polydisulfide dendrimer nanoclusters (DNCs) labelled with
Gd chelates have been tested as MRI contrast agents. Gd was found to accu-
mulate in various organs of mice including heart, lung, liver, kidney, spleen,
and blood 24 h post-injection with the highest uptake observed in the kidney
(5.68 2.32 % I.D./g) followed by liver (4.52 1.93 % I.D./g) and then the
spleen (2.95 1.36 % I.D./g). Polydisulide DNCs exhibited a circulation half-
life of >1.6 h in mice with considerable contrast enhancement in the abdominal
aorta and kidneys for around 4 h. T1-weighted images of kidneys and abdominal
aorta showed a significant contrast enhancement after 15 min and 1 h post-injec-
tion of Polydisulfide DNCs compared to G3 PAMAM dendrimers (Fig.
9
) (Huang
et al. 2012).
All the above stated examples clearly implicate that the road towards improve-
ment in efficiency of dendrimer-based contrast agents will increase their avail-
ability for clinical applications. Perhaps a new horizon could be combining the
molecular contrast agents and therapeutic payloads in a single dendrimer molecule
to achieve imaging of malignant tissue for therapeutic benefit.
