364
N. Ashwin Kumar et al.
targeting moiety mannose compared with control Gd-DTPA. T 1 MR imaging with
mannose Gd-DTPA showed increase macrophages uptake both in vitro and in vivo
with less toxicity in organs. Discrimination of severity of the inflammation was
revealed with T 1 MR images using these Gd loaded nanoliposomes. Detecting the
absence of specific tumor markers in cancer cells is challenging until now, especially
for triple-negative markers in breast cancer cells. Without these markers such as HER2, estrogen, and progesterone hormones, and it is challenging to treat metastatic cells
[165]. To address this issue, Schroeder and his coworkers developed targeted nanoliposomes (100 nm) to detect the remaining metastatic breast cancer cells post-surgery
[166]. Triple-negative metastatic breast cancer cells were injected via tail vein (4T1
cells) and then treated with multi-modal imaging contrast to image the small lesion.
Gadolinium loaded liposomes detect the premetastatic niche in 9 and 15 days and
micrometastasis in the later stages. The small lesion images from MR were further
confirmed by H&E staining of lungs.
Thermosensitive based liposomes (TSL) are promising drug carrier particles for
drug delivery when the heat is generated by external sources of localized hyperthermia [24]. In 2015, Kuijten et al. synthesized biotin TSL loaded with imaging
molecules and drug moieties in the hydrophilic regions. This work was developed
to increase the relaxivity of MR agents rather than increasing the concentration of
Gd
3+ agents. Gd-DOTA linked with pegylated lipid functionalized with biotin and
loaded with rhodamine (NLP) compared with conventional liposomes Gd-DTPABSA with pegylated lipid (CLP) [167]. The heat generated from TSL causes a
change in the behavior of water molecules into NLP that changes the relaxivity of
Gd-DOTA. MR/Optical based image-guided TSL would help using external sources
like hyperthermia and ultrasound-mediated drug delivery for solid tumors. Also, biomagnetic properties like Gd
3+ chelates (paramagnetic) and iron oxide nanoparticles
(super-paramagnetic) was loaded into TSL for MR guided imaging. This TSL was
exposed to highly focused ultrasound for increased relaxivity, as mentioned earlier.
Co-labeled magnetic properties help physicians to select suitable MR sequences
to study the accumulation and image-guided drug delivery of liposomes [168].
Delivery of membrane-impermeable drugs like gemcitabine (GEM) into solid tumors
is challenging. Affram et al. synthesized TSL based particles loaded with GEM
and Magnevist for effective image-guided drug delivery triggered via localized heat
sources on an ex vivo model [169].
Apart from chelates of Gd
3+ used as MR contrast, oxides of Gadolinium in
nanometer-sized particles were synthesized and developed as MR contrast agents.
Udayal developed the first synthesis of Gd 2 O 3 nanoparticle with a size of ~ 5 nm, and
his coworkers showed high T 1 relaxivity. Furthermore, pegylated-Gd 2 O 3 nanoparticles were characterized by MR imaging having 4 times higher than the Gd-DTPA
contrast [170, 171]. Glioblastoma cell labeled ultrasmall diethylene glycol capped
Gd 2 O 3 NPs (2–3 nm) were implanted in chicken embryo and studied the tumor
growth in clinical MRI [172]. Agglomeration of Gd 2 O 3 NPs has an impact on
the change in the relaxation properties in NMR signals. Particles showed enhanced
signals in non-agglomerated particles compared to agglomerated ones when imaged
through MR 1.5 and 7 T [173]. Park et al. suggested that depending upon the particle
N. Ashwin Kumar et al.
targeting moiety mannose compared with control Gd-DTPA. T 1 MR imaging with
mannose Gd-DTPA showed increase macrophages uptake both in vitro and in vivo
with less toxicity in organs. Discrimination of severity of the inflammation was
revealed with T 1 MR images using these Gd loaded nanoliposomes. Detecting the
absence of specific tumor markers in cancer cells is challenging until now, especially
for triple-negative markers in breast cancer cells. Without these markers such as HER2, estrogen, and progesterone hormones, and it is challenging to treat metastatic cells
[165]. To address this issue, Schroeder and his coworkers developed targeted nanoliposomes (100 nm) to detect the remaining metastatic breast cancer cells post-surgery
[166]. Triple-negative metastatic breast cancer cells were injected via tail vein (4T1
cells) and then treated with multi-modal imaging contrast to image the small lesion.
Gadolinium loaded liposomes detect the premetastatic niche in 9 and 15 days and
micrometastasis in the later stages. The small lesion images from MR were further
confirmed by H&E staining of lungs.
Thermosensitive based liposomes (TSL) are promising drug carrier particles for
drug delivery when the heat is generated by external sources of localized hyperthermia [24]. In 2015, Kuijten et al. synthesized biotin TSL loaded with imaging
molecules and drug moieties in the hydrophilic regions. This work was developed
to increase the relaxivity of MR agents rather than increasing the concentration of
Gd
3+ agents. Gd-DOTA linked with pegylated lipid functionalized with biotin and
loaded with rhodamine (NLP) compared with conventional liposomes Gd-DTPABSA with pegylated lipid (CLP) [167]. The heat generated from TSL causes a
change in the behavior of water molecules into NLP that changes the relaxivity of
Gd-DOTA. MR/Optical based image-guided TSL would help using external sources
like hyperthermia and ultrasound-mediated drug delivery for solid tumors. Also, biomagnetic properties like Gd
3+ chelates (paramagnetic) and iron oxide nanoparticles
(super-paramagnetic) was loaded into TSL for MR guided imaging. This TSL was
exposed to highly focused ultrasound for increased relaxivity, as mentioned earlier.
Co-labeled magnetic properties help physicians to select suitable MR sequences
to study the accumulation and image-guided drug delivery of liposomes [168].
Delivery of membrane-impermeable drugs like gemcitabine (GEM) into solid tumors
is challenging. Affram et al. synthesized TSL based particles loaded with GEM
and Magnevist for effective image-guided drug delivery triggered via localized heat
sources on an ex vivo model [169].
Apart from chelates of Gd
3+ used as MR contrast, oxides of Gadolinium in
nanometer-sized particles were synthesized and developed as MR contrast agents.
Udayal developed the first synthesis of Gd 2 O 3 nanoparticle with a size of ~ 5 nm, and
his coworkers showed high T 1 relaxivity. Furthermore, pegylated-Gd 2 O 3 nanoparticles were characterized by MR imaging having 4 times higher than the Gd-DTPA
contrast [170, 171]. Glioblastoma cell labeled ultrasmall diethylene glycol capped
Gd 2 O 3 NPs (2–3 nm) were implanted in chicken embryo and studied the tumor
growth in clinical MRI [172]. Agglomeration of Gd 2 O 3 NPs has an impact on
the change in the relaxation properties in NMR signals. Particles showed enhanced
signals in non-agglomerated particles compared to agglomerated ones when imaged
through MR 1.5 and 7 T [173]. Park et al. suggested that depending upon the particle