theranostic applications [13]. Khan et al. reported the therapeutic efficacy of
198
Au
composite nano-devices in mouse melanoma tumor model by intratumoral injection
of the NPs [14]. Chanda et al. reported that gum arabic glycoprotein (GA)-functionalized
198 Au showed therapeutic effect in mouse prostate cancer model after
intratumoral injection of the NPs. They also showed the biocompatibility of their
approach by showing no or minimal leakage of the NPs and no pathologic change
in blood cells after the treatment [12]. In 2012, Shukla et al. developed prostate
tumor specific epigallocatechin-gallate (EGCg) functionalized
198 Au (
198
Au
NP-EGCg). In this study,
198 Au NP-EGCg was injected in prostate cancer mouse
model. Approximately 72% NPs were retained in the tumor after 24 h and 80% of
the tumor volume was reduced after 28 days [15].
11.3 Functionalization of Nanoparticles
In radionanomedicine trace amounts of radiolabeled NPs can be used for in vivo
theragnosis. This requires increasing the specific delivery of NPs to the target
tissues while decreasing the nonspecific binding to normal tissues, which was
proven to be difficult to achieve in practice. The biological properties of NPs
depend on the ligands attached to their surfaces, and targeting ligands as well as
polyethylene glycol (PEG) molecules are used to reduce the nonspecific
normal-tissue uptake [60]. Surface modification of NPs to produce the
well-functionalized NPs should focus on the ligand selection and PEG. However,
the conventional method, which adopts multistep and step-by-step approach for
surface modification of NPs, has many difficulties necessitating a novel method and
recently several methods came to be available to overcome these difficulties.
11.3.1 PEGylation
The majority of the NPs have hydrophobic surfaces after the core synthesis. So the
use of PEG or natural and synthetic polymers including dextran is necessary for
making the surface hydrophilic and retaining the material’s stability in a biological
environment [61]. The addition of PEG to the NPs’ surface reduce reticuloendothelial system uptake of NPs, NPs’ interaction with small molecules, and their
aggregation, and thus increase circulation time, solubility in serum, and enhanced
permeability and retention (EPR) effect [62–64]. Using the PEGylation technique
Doxil
® (liposomal delivery vehicle for doxorubicin) and Oncospar
® (PEG-Lasparaginase) became the first FDA-approved NP therapeutics [65]. PEGylation
yielded the drug half-life of 72 h with the circulation half-life of 36 h.
11 Radiolabeling Method: Core/Surface Labeling, Chemical …
213
198
Au
composite nano-devices in mouse melanoma tumor model by intratumoral injection
of the NPs [14]. Chanda et al. reported that gum arabic glycoprotein (GA)-functionalized
198 Au showed therapeutic effect in mouse prostate cancer model after
intratumoral injection of the NPs. They also showed the biocompatibility of their
approach by showing no or minimal leakage of the NPs and no pathologic change
in blood cells after the treatment [12]. In 2012, Shukla et al. developed prostate
tumor specific epigallocatechin-gallate (EGCg) functionalized
198 Au (
198
Au
NP-EGCg). In this study,
198 Au NP-EGCg was injected in prostate cancer mouse
model. Approximately 72% NPs were retained in the tumor after 24 h and 80% of
the tumor volume was reduced after 28 days [15].
11.3 Functionalization of Nanoparticles
In radionanomedicine trace amounts of radiolabeled NPs can be used for in vivo
theragnosis. This requires increasing the specific delivery of NPs to the target
tissues while decreasing the nonspecific binding to normal tissues, which was
proven to be difficult to achieve in practice. The biological properties of NPs
depend on the ligands attached to their surfaces, and targeting ligands as well as
polyethylene glycol (PEG) molecules are used to reduce the nonspecific
normal-tissue uptake [60]. Surface modification of NPs to produce the
well-functionalized NPs should focus on the ligand selection and PEG. However,
the conventional method, which adopts multistep and step-by-step approach for
surface modification of NPs, has many difficulties necessitating a novel method and
recently several methods came to be available to overcome these difficulties.
11.3.1 PEGylation
The majority of the NPs have hydrophobic surfaces after the core synthesis. So the
use of PEG or natural and synthetic polymers including dextran is necessary for
making the surface hydrophilic and retaining the material’s stability in a biological
environment [61]. The addition of PEG to the NPs’ surface reduce reticuloendothelial system uptake of NPs, NPs’ interaction with small molecules, and their
aggregation, and thus increase circulation time, solubility in serum, and enhanced
permeability and retention (EPR) effect [62–64]. Using the PEGylation technique
Doxil
® (liposomal delivery vehicle for doxorubicin) and Oncospar
® (PEG-Lasparaginase) became the first FDA-approved NP therapeutics [65]. PEGylation
yielded the drug half-life of 72 h with the circulation half-life of 36 h.
11 Radiolabeling Method: Core/Surface Labeling, Chemical …
213