modification process makes the production procedure cumbersome and delivers a
low final yield. Hence, a breakthrough in this particular field was necessary.
11.3.3 Micelle Encapsulation
The conventional method for functionalizing the NPs, which is a multistep and
step-by-step approach for surface modification of NPs, has many difficulties. First
of all, the multistep chemical reactions can cause decreasing total yield of modified
NPs. In addition, in each reaction step, we have to consider the reaction time,
temperature, pH, impurities, solvents, reagent concentrations, etc. Sometimes, a
complicated situation can be induced by the conjugation of two or more ligands.
Such difficulties necessitated a novel method, which we think is micelle encapsulation method.
Hydrophilization of NPs using the micelle encapsulation method was first
pro-posed by Dubertret et al. [83]. This method evolved from the use of a two-tailed
phospholipid to the use of a one-tailed C-12 alkanethiol [84]. Fan and colleagues
introduced microencapsulation and the solvent evaporation method, which was
optimized to a quick and simple method [85] (Fig. 11.2a). The Dubertret’s group,
again using a two-tailed phospholipid, successfully introduced recently functional
biomolecules [86]. Wu and colleagues produced micelles by adopting PEG sorbitan
fatty acid esters [87] (Fig. 11.2b). Recently, Jeong’s group integrated these
developments to make a quick and straightforward method of mixing, sonicating,
and size exclusion chromatography for producing functionally active multi-specific
NPs [48] (Fig. 11.2c). This should be the ultimate solution to the challenge posed in
radiolabeling of functional NPs. Jeong ingeniously proposed this one-step method
under mild conditions to preserve ligand integrity, which is now called the
micelle-encapsulation method [48, 78]. This method was inspired by the
hydrophilization method used for quantum dots (QD) [83, 86], surface-enhanced
Raman scattering (SERS) dots [88], QD-embedded silica NPs [89], gold or iron
oxide NPs [84, 90], or other hydrophobic NPs, which were also found to be the
appropriate core for encapsulation.
Jeong’s contribution relies on the use of combined multiplex amphiphiles with
different functional groups simultaneously to achieve surface multifunctionality and
hydrophilicity of NPs (Fig. 11.3). In the micelle-encapsulation method, the ligands
and the chelator as well as the PEGs are specifically prepared to form a micelle. The
micelle in the aqueous phase is then mixed with the NPs in the lipid phase and
sonicated to yield the encapsulated NPs. The final multiplexed NPs were purified by
size exclusion chromatography. If the small molecules such as mannose, lactose, or
cRGD (cyclic Arginine-Glycine-Aspartate) were to be used as ligands, these
ligands were covalently bound to the tip of an alkyl chain of optimal length. Using
this method, Lee et al. labeled QD544T with
68 Ga and added functional group of
RGD and showed specific targeted imaging of
68 Ga-NOTA-QD655T-RGD in
glioma tumor mouse model [48]. Figure 11.4 depicts the dimension of the modifier
11 Radiolabeling Method: Core/Surface Labeling, Chemical …
215
low final yield. Hence, a breakthrough in this particular field was necessary.
11.3.3 Micelle Encapsulation
The conventional method for functionalizing the NPs, which is a multistep and
step-by-step approach for surface modification of NPs, has many difficulties. First
of all, the multistep chemical reactions can cause decreasing total yield of modified
NPs. In addition, in each reaction step, we have to consider the reaction time,
temperature, pH, impurities, solvents, reagent concentrations, etc. Sometimes, a
complicated situation can be induced by the conjugation of two or more ligands.
Such difficulties necessitated a novel method, which we think is micelle encapsulation method.
Hydrophilization of NPs using the micelle encapsulation method was first
pro-posed by Dubertret et al. [83]. This method evolved from the use of a two-tailed
phospholipid to the use of a one-tailed C-12 alkanethiol [84]. Fan and colleagues
introduced microencapsulation and the solvent evaporation method, which was
optimized to a quick and simple method [85] (Fig. 11.2a). The Dubertret’s group,
again using a two-tailed phospholipid, successfully introduced recently functional
biomolecules [86]. Wu and colleagues produced micelles by adopting PEG sorbitan
fatty acid esters [87] (Fig. 11.2b). Recently, Jeong’s group integrated these
developments to make a quick and straightforward method of mixing, sonicating,
and size exclusion chromatography for producing functionally active multi-specific
NPs [48] (Fig. 11.2c). This should be the ultimate solution to the challenge posed in
radiolabeling of functional NPs. Jeong ingeniously proposed this one-step method
under mild conditions to preserve ligand integrity, which is now called the
micelle-encapsulation method [48, 78]. This method was inspired by the
hydrophilization method used for quantum dots (QD) [83, 86], surface-enhanced
Raman scattering (SERS) dots [88], QD-embedded silica NPs [89], gold or iron
oxide NPs [84, 90], or other hydrophobic NPs, which were also found to be the
appropriate core for encapsulation.
Jeong’s contribution relies on the use of combined multiplex amphiphiles with
different functional groups simultaneously to achieve surface multifunctionality and
hydrophilicity of NPs (Fig. 11.3). In the micelle-encapsulation method, the ligands
and the chelator as well as the PEGs are specifically prepared to form a micelle. The
micelle in the aqueous phase is then mixed with the NPs in the lipid phase and
sonicated to yield the encapsulated NPs. The final multiplexed NPs were purified by
size exclusion chromatography. If the small molecules such as mannose, lactose, or
cRGD (cyclic Arginine-Glycine-Aspartate) were to be used as ligands, these
ligands were covalently bound to the tip of an alkyl chain of optimal length. Using
this method, Lee et al. labeled QD544T with
68 Ga and added functional group of
RGD and showed specific targeted imaging of
68 Ga-NOTA-QD655T-RGD in
glioma tumor mouse model [48]. Figure 11.4 depicts the dimension of the modifier
11 Radiolabeling Method: Core/Surface Labeling, Chemical …
215