therapeutic drugs to the tumors, using liposome [21, 22], iron oxide nanoparticles
[23], or gold nanoparticles [24], etc.
Carbohydrates are another class of small molecules requiring targeting ligands
that selectively recognize cell surface receptors, such as mannose receptor (cluster
of differentiation or classification determinant 206, CD 206) or asialoglycoprotein
receptor (ASGP-R). Lymphoseek (
99m Tc-tilmanocept) is the
99m Tc labeled
nanocomposite using dextran polymer decorated mannose molecules on it, which
can target the mannose receptor of monocytes/macrophages homing to lymph nodes
and has the clinical indication for lymphatic mapping with a hand-held gamma
counter to assist in the localization of lymph nodes draining the primary tumor in
patients with breast cancer or melanoma [25]. Jeong et al. reported the
99m Tc
labeled mannosylated albumin nanoparticles for sentinel node detection with targeting mannose receptor of monocytes on lymph node [26]. In this study, they
could find the specific targeting ability of
99m
Tc-mannosylated human serum
albumin (MSA) to the lymphatic system (14.0%ID/organ at 1 h post-injection), on
the other hand,
99m Tc-human serum albumin (HSA) showed low uptake (2.4%ID/
organ at 1 h post-injection). Recently, they developed the
68 Ga version of MSA
nanoparticles for targeting mannose receptors on monocytes/macrophages in the
myocardium after the induction of myocardial inflammation using myocarditis
model in animals [27]. Another examples of mannose-tagged iron oxide nanoparticles for lymph node imaging using multimodal positron emission tomography
(PET) and magnetic resonance imaging (MRI) has been also addressed [13].
Galactose is the potential ligand for the target of ASGP-R, which is highly
expressed on hepatocyte [28, 29], and Lee et al. clearly showed the targeting ability
of galactose-conjugated superparamagnetic iron oxide nanoparticles (SPION) to the
hepatocyte in the liver using in vivo animal model [30].
Folic acid (folate) receptors, a glycosylphosphatidylinositol-anchored cell surface receptor, is overexpressed on the vast majority of cancer tissues, while its
expression is limited in healthy tissues and organs, therefore, folate can be used as a
target molecule for targeted delivery of imaging and therapeutic agents to tumors
[31]. Lu et al. demonstrated the targeting and therapeutic efficacy of folate-tagged
mesoporous silica nanoparticles [32].
The extracellular domain of prostate-specific mem-brane antigen (PSMA, also
known as folate hydrolase 1 or glutamate carboxypeptidase II) has gained
increasing interest for imaging and therapeutic target of prostate cancer [33]. From
the great success of
68
Ga labeled PSMA inhibitor,
68 Ga-glutamate-urea-lysine
(EuK) derivatives [34], numerous nanoparticles conjugated with EuK have been
developed for imaging and therapy of prostate cancer. Sachin et al. have established
the docetaxel encapsulated into poly(lactide-b-ethylene glycol-b-lactide)
(PLA-PEG-PLA) nanoparticles with the decoration of EuK as a PSMA targeting
molecules, and showed the specific uptake in PSMA positive, LNCaP cell-lines
[35]. Moon et al. also showed the specific uptake of EuK-tagged iron oxide
nanoparticles (IONP) in the tumor bearing mouse model using PET/MR dual
modality [14]. Another approach of EuK-tagged docetaxel-containing nanoparticle,
BIND-014 is now under Phase 1 clinical study [36].
236
Y.-S. Lee et al.
[23], or gold nanoparticles [24], etc.
Carbohydrates are another class of small molecules requiring targeting ligands
that selectively recognize cell surface receptors, such as mannose receptor (cluster
of differentiation or classification determinant 206, CD 206) or asialoglycoprotein
receptor (ASGP-R). Lymphoseek (
99m Tc-tilmanocept) is the
99m Tc labeled
nanocomposite using dextran polymer decorated mannose molecules on it, which
can target the mannose receptor of monocytes/macrophages homing to lymph nodes
and has the clinical indication for lymphatic mapping with a hand-held gamma
counter to assist in the localization of lymph nodes draining the primary tumor in
patients with breast cancer or melanoma [25]. Jeong et al. reported the
99m Tc
labeled mannosylated albumin nanoparticles for sentinel node detection with targeting mannose receptor of monocytes on lymph node [26]. In this study, they
could find the specific targeting ability of
99m
Tc-mannosylated human serum
albumin (MSA) to the lymphatic system (14.0%ID/organ at 1 h post-injection), on
the other hand,
99m Tc-human serum albumin (HSA) showed low uptake (2.4%ID/
organ at 1 h post-injection). Recently, they developed the
68 Ga version of MSA
nanoparticles for targeting mannose receptors on monocytes/macrophages in the
myocardium after the induction of myocardial inflammation using myocarditis
model in animals [27]. Another examples of mannose-tagged iron oxide nanoparticles for lymph node imaging using multimodal positron emission tomography
(PET) and magnetic resonance imaging (MRI) has been also addressed [13].
Galactose is the potential ligand for the target of ASGP-R, which is highly
expressed on hepatocyte [28, 29], and Lee et al. clearly showed the targeting ability
of galactose-conjugated superparamagnetic iron oxide nanoparticles (SPION) to the
hepatocyte in the liver using in vivo animal model [30].
Folic acid (folate) receptors, a glycosylphosphatidylinositol-anchored cell surface receptor, is overexpressed on the vast majority of cancer tissues, while its
expression is limited in healthy tissues and organs, therefore, folate can be used as a
target molecule for targeted delivery of imaging and therapeutic agents to tumors
[31]. Lu et al. demonstrated the targeting and therapeutic efficacy of folate-tagged
mesoporous silica nanoparticles [32].
The extracellular domain of prostate-specific mem-brane antigen (PSMA, also
known as folate hydrolase 1 or glutamate carboxypeptidase II) has gained
increasing interest for imaging and therapeutic target of prostate cancer [33]. From
the great success of
68
Ga labeled PSMA inhibitor,
68 Ga-glutamate-urea-lysine
(EuK) derivatives [34], numerous nanoparticles conjugated with EuK have been
developed for imaging and therapy of prostate cancer. Sachin et al. have established
the docetaxel encapsulated into poly(lactide-b-ethylene glycol-b-lactide)
(PLA-PEG-PLA) nanoparticles with the decoration of EuK as a PSMA targeting
molecules, and showed the specific uptake in PSMA positive, LNCaP cell-lines
[35]. Moon et al. also showed the specific uptake of EuK-tagged iron oxide
nanoparticles (IONP) in the tumor bearing mouse model using PET/MR dual
modality [14]. Another approach of EuK-tagged docetaxel-containing nanoparticle,
BIND-014 is now under Phase 1 clinical study [36].
236
Y.-S. Lee et al.